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Biochemistry & Molecular Biology - Biochimie - Biochimica

SIMPLE CONTENTS

NEWS & UPDATES
MAPS
OVERVIEW
CHEMISTRY
BIOMOLECULES
CELLULAR
METABOLISM & HOMEOSTASIS
ENZYMES
ENERGY METABOLISM
CARBOHYDRATE METABOLISM
LIPID METABOLISM
NITROGEN METABOLISM - NUCLEOTIDE - AMINO ACIDS
INTEGRATION OF METABOLISM - FED VERSUS UNFED STATE
NUTRITION - VITAMINS
MOLECULAR - NUCLEOTIDE SYNTHESIS - GENE EXPRESSION - REPLICATION -  MUTATIONS & DNA REPAIR
PLANT BIOCHEMISTRY
PROTEIN BIOSYNTHESIS, MODIFICATIONS & DEGRADATION - TRANSCRIPTION - TRANSLATION
MEMBRANE BIOCHEMISTRY, TRANSPORT,  SIGNAL TRANSDUCTION
TISSUES & ORGANS - CONNECTIVE TISSUE
GENETICS
CLINICAL
TECHNIQUES IN BIOCHEMISTRY, MOLECULAR BIOLOGY & GENETICS
COMMON LABORATORY VALUES
REFERENCES

TOC
DETAILED CONTENTS

MAPS
OVERVIEW

CHEMISTRY

CHEMISTRY OF BIOMOLECULES - CARBOHYDRATES, LIPIDS, & AMINO ACIDS : METABOLIC FUELS & BIOSYNTHETIC PRECURSORS
CARBOHYDRATES
AMINO ACIDS, PEPTIDES & PROTEINS
COFACTORS
LIPIDS
NUCLEOTIDES & NUCLEIC ACIDS
ENERGY

CELLULAR - ORGANELLES
BIOLOGICAL MEMBRANES

METABOLISM
ACID - BASE RELATIONSHIPS
OVERVIEW OF METABOLISM

ENZYMES

METABOLIC REGULATION
INTERMEDIARY METABOLISM
REGULATORY MECHANISMS
ALLOSTERIC REGULATION
TRANSCRIPTION CONTROL
HORMONAL CONTROL

ENERGY METABOLISM - BIOENERGETICS - CITRIC ACID CYCLE → OXIDATIVE PHOSPHORYLATION = ELECTRON TRANSPORT CHAIN + ATP SYNTHASE

CARBOHYDRATE METABOLISM - GLYCOLYSIS → PYRUVATE DECARBOXYLATION →  CITRIC ACID CYCLE
INTRODUCTION TO CARBOHYDRATES
INTRODUCTION TO METABOLISM & GLYCOLYSIS
TRICARBOXYLIC ACID CYCLE & PYRUVATE DEHYDROGENASE
GLUCONEOGENESIS
GLYCOGEN METABOLISM
METABOLISM OF MONOSACCHARIDES & DISACCHARIDES
PENTOSE PHOSPHATE PATHWAY & NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE
GLYCOSAMINOGLYCANS, PROTEOGLYCANS, & GLYCOPROTEINS

LIPID METABOLISM & GLYCOLIPIDS
DIETARY LIPID METABOLISM
FATTY ACID, TRIACYLGLYCEROL, & KETONE BODY METABOLISM
PHOSPHOLIPID, GLYCOSPHINGOLIPID, & EICOSANOID METABOLISM
CHOLESTEROL, LIPOPROTEIN, & STEROID METABOLISM - STEROIDS & ISOPRENOIDS

NITROGEN METABOLISM
PROTEIN METABOLISM - AMINO ACID METABOLISM & DERIVATIVES
AMINO ACIDS : NITROGEN DISPOSAL
AMINO ACID DEGRADATION & SYNTHESIS
AMINO ACIDS : CONVERSION TO SPECIALIZED PRODUCTS
TETRAPYRROLES - PORPHYRINS - HAEM
NUCLEOTIDE METABOLISM - NUCLEOTIDES & NUCLEOSIDES

INTEGRATION OF METABOLISM
METABOLIC EFFECTS OF INSULIN & GLUCAGON
FED VERSUS UNFED STATE - THE FEED-FAST CYCLE
DIABETES MELLITUS
OBESITY

NUTRITION
MACRONUTRIENTS
COFACTORS & VITAMINS
MINERALS

MOLECULAR BIOLOGY - STORAGE & EXPRESSION OF GENETIC INFORMATION - GENE EXPRESSION
OVERVIEW OF GENE EXPRESSION
GENETIC INFORMATION
DNA AND RNA : NUCLEIC ACID STRUCTURE
DNA SYNTHESIS (REPLICATION)
TRANSCRIPTION
TRANSLATION (PROTEIN SYNTHESIS)
MUTATIONS

BACTERIA
NUCLEIC ACID METABOLISM IN BACTERIA
BACTERIAL DNA REPLICATION
BACTERIAL DNA REPAIR
DEGRADATION OF NUCLEIC ACIDS

EUKARYA
NUCLEIC ACID METABOLISM IN EUKARYA - DNA STRUCTURE, REPLICATION, & REPAIR
ORGANIZATION OF EUKARYOTIC DNA SUPERCOILING
EUKARYOTIC DNA REPLICATION
EUKARYOTIC DNA REPAIR
MUTATIONS & DNA REPAIR

BACTERIA
SPECIAL BACTERIAL METABOLISM & BIOSYNTHESIS OF ANTIMICROBIALS

PLANT
PHOTOSYNTHESIS
PLANT SECONDARY METABOLISM
 
OTHER
METAL METABOLISM
IRON METABOLISM
ETHANOL METABOLISM
PHOSPAGEN SYSTEM (ATP-PCR)

PROTEIN BIOSYNTHESIS, MODIFICATIONS & DEGRADATION

BACTERIA
PROTEIN SYNTHESIS IN BACTERIA
BACTERIAL TRANSCRIPTION
REGULATION OF BACTERIAL GENE EXPRESSION
BACTERIAL PROTEIN SYNTHESIS
DEGRADATION OF NUCLEIC ACIDS

EUKARYA
PROTEIN BIOSYNTHESIS IN EUKARYA - RNA STRUCTURE, SYNTHESIS = TRANSCRIPTION & PROCESSING - PROTEIN SYNTHESIS = TRANSLATION
EUKARYOTIC TRANSCRIPTION
REGULATION OF EUKARYOTIC TRANSCRIPTION
EUKARYOTIC TRANSLATION
TRANSLATIONAL REGULATION
mRNA DEGRADATION

REGULATION OF GENE EXPRESSION

CELL CYCLE IN EUKARYA

POSTTRANSLATIONAL MODIFICATION OF PROTEINS
PROTEIN PROCESSING IN THE ENDOPLASMIC RETICULUM
GLYCOSYLATION REACTIONS IN THE GOLGI APPARATUS
TERMINAL CARBOHYDRATE STRUCTURES OF GLYCOCONJUGATES

PROTEIN FOLDING, TRANSPORT / TARGETING & DEGRADATION
FOLDING OF PROTEINS
VESICULAR TRANSPORT & SECRETION OF PROTEINS
PROTEIN TRANSPORT INTO THE NUCLEUS
PROTEIN TRANSPORT INTO MITOCHONDRIA
PROTEIN TRANSPORT INTO CHLOROPLASTS
PROTEIN DEGRADATION
PROTEIN DEGRADATION BY THE UBIQUITIN-PROTEASOME SYSTEM (UPS)

VIRUSES

TRANSPORT - MEMBRANE BIOCHEMISTRY, SIGNAL TRANSDUCTION

TRANSPORT THROUGH MEMBRANES

TRANSPORT OF LIPIDS IN PLASMA

OXYGEN TRANSPORT BY HEMOGLOBIN

SIGNAL TRANSDUCTION & CELLULAR COMMUNICATION

INTERCELLULAR SIGNAL TRANSMISSION BY HORMONES - WATER-SOLUBLE - CATECHOLAMINE PEPTIDE PROTEIN
FUEL METABOLISM : INSULIN & GLUCAGON - EPINEPHRINE & (NOREPINEPHRINE) - CORTISOL
HYPOTHALAMUS-ANTERIOR PITUITARY HORMONE SYSTEM
PLACENTAL
EXTRACELLULAR CA++, MG++ & PHOSPHATE CONCENTRATIONS : PTH - CALCITRIOL,
NA+ CONCENTRATION & WATER BALANCE : ALDOSTERONE - ARGININE VASOPRESSIN (AVP) = ADH
BODY SIZE & METABOLISM : THYROXINE & TRIIODOTHYRONINE - HGH
MALE : TESTOSTERONE - FSH - LH
FEMALE : ESTRADIOL - PROGESTERONE - PROLACTIN - OXYTOCIN
GASTROINTESTINAL TRACT

NERVE CONDUCTION & SYNAPTIC TRANSMISSION
POSTSYNAPTIC RECEPTORS

PRINCIPLES OF INTRACELLULAR COMMUNICATION

RECEPTORS COUPLED TO HETEROTRIMERIC G-PROTEINS
MUSCLE CONTRACTION
VISUAL PROCESS
OLFACTORY & GUSTATORY PROCESSES
ARACHIDONATE METABOLISM & EICOSANOIDS

RECEPTORS ACTING THROUGH TYROSINE KINASES

PROGRAMMED CELL DEATH (APOPTOSIS)

RECEPTORS FOR STEROID & THYROID HORMONES, FOR RETINOIDS & VITAMIN D - LIPID-SOLUBLE - STEROID THYROID

CYCLIC GMP DEPENDENT PATHWAYS & EFFECTS OF NITRIC OXIDE (NO)

TISSUES & ORGANS

DIGESTION

BLOOD
BLOOD COAGULATION & FIBRINOLYSIS - BLOOD CLOTTING
HEMOSTASIS
INITIAL REACTIONS
COAGULATION PROPAGATION & CONTROL
PLATELETS (THROMBOCYTES)
FIBRINOLYSIS

IMMUNE SYSTEM
COMPONENTS OF THE IMMUNE SYSTEM
GENERATION OF A SPECIFIC IMMUNE RESPONSE
PATHOLOGIC IMMUNE RESPONSES
ADHESION OF LEUKOCYTES

LIVER

KIDNEY

MUSCLE

CONNECTIVE

BRAIN & SENSORY

HORMONES

GENETICS

CLINICAL BIOCHEMISTRY

LABORATORY TECHNIQUES IN BIOCHEMISTRY, MOLECULAR BIOLOGY & GENETICS - BIOTECHNOLOGY & HUMAN DISEASE

COMMON LABORATORY VALUES

REFERENCES

TOC
MAPS

TOC
OVERVIEW
(Wilcox HY 2009, Contents) V1 PDF
(Tellingen Phenomenology, Contents) V1 JPG
(Koolman Atlas 2012) V1 PDF
(Sutton, Chemistry) V1 PDF
(Caratini Collection, Chimie Organique et Biochimie) V1 PDF
(Toussaint PACES 2015 Chimie et Biochimie, Sommaire Détaillé) V1 PDF
(Hecketsweiler, Sommaire) V1 PDF
(Hecketsweiler, Résumé des Métabolismes & Formules Chimiques) V1 PDF

TOC
CHEMISTRY
PHYSICAL CHEMISTRY
ORGANIC CHEMISTRY
GENERAL BIOCHEMISTRY

TOC  
BIOMOLECULES
Biosphere > Biome > Ecosystem > Biocoenosis > Population > Organism > Organ system > Organ > Tissue > Cell > Organelle > Biomolecular complex > Macromolecule > Biomolecule
LIGNIN

TOC
CARBOHYDRATES - CHEMISTRY & STRUCTURE
(Hecketsweiler, Glucides Formules) V1 JPG

CARBOHYDRATES
CLASSIFICATION
CYCLIC STRUCTURES 
MUTAROTATION
MONOSACCHARIDES
IMPORTANT PROPERTIES OF MONOSACCHARIDES 
OTHER SUGAR DERIVATIVES OF BIOMEDICAL IMPORTANCE
DISACCHARIDES
OLIGOSACCHARIDES
POLYSACCHARIDES
HETEROPOLYSACCHARIDES (HETEROGLYCANS)
MUCOPOLYSACCHARIDES (MPS) 
PROTEOGLYCANS—CHEMISTRY AND FUNCTIONS

OVERVIEW
MONOSACCHARIDES
MONOSACCHARIDE DERIVATIVES
COMMON DISACCHARIDES
POLYSACCHARIDES

STRUCTURE & CLASSIFICATION
GLYCOSIDIC BONDS

TOC
AMINO ACIDS & PROTEINS - CHEMISTRY & STRUCTURE
Primary Secondary Tertiary Quaternary Determination Prediction Design Thermodynamics
(Hecketsweiler, Proteines Formules) V1 JPG 1 - V1 JPG 2

CHEMISTRY OF PROTEINS AND AMINO ACIDS
AMINO ACIDS
PROTEINS
GENERAL PROPERTIES OF PROTEINS
STRUCTURAL ORGANISATION OF PROTEINS
DENATURATION OF PROTEINS
AMINOACIDURIAS

AMINO ACIDS

OVERVIEW
STRUCTURE & CLASSIFICATION
PEPTIDE BONDS
ACID-BASE PROPERTIES OF AMINO ACIDS
MODIFICATION OF AMINO ACID RESIDUES IN PROTEINS

PROTEINS

FUNCTIONS OF PROTEINS
Enzyme catalysis
Transport
Storage
Motion
Structural & mechanical support
Defense
Signal transduction
Control of growth, differentiation and metabolism
Toxin
Binding of molecules
Transport of molecules across cellular membranes
Coordinated movement of cells and cellular structures

PROTEINS AS POLYPEPTIDES

PROTEIN STRUCTURE - HIERARCHICAL STRUCTURE OF PROTEINS
OVERVIEW
PRIMARY STRUCTURE
SECONDARY STRUCTURE
TERTIARY STRUCTURE
QUATERNARY STRUCTURE
QUATERNARY STRUCTURE
PROTEIN DENATURATION

PROTEIN SOLUBILITY AND R-GROUPS
PROTEIN DENATURATION
CLINICAL RELEVANCE

PLASMA PROTEINS—CHEMISTRY AND FUNCTIONS
PLASMA PROTEINS
CHARACTERISTICS OF INDIVIDUAL PLASMA PROTEINS
OTHER PROTEINS OF CLINICAL INTEREST
•FUNCTIONS OF PLASMA PROTEINS
GENETIC DEFICIENCIES OF PLASMA PROTEINS
PROTEINURIA

IMMUNOGLOBULINS—CHEMISTRY AND FUNCTIONS
PROPERTIES OF INDIVIDUAL IMMUNOGLOBULINS
STRUCTURE AND CHEMISTRY OF IMMUNOGLOBULINS—MODEL OF IG MOLECULE
POLYCLONAL VS MONOCLONAL ANTIBODY: HYBRIDOMA

HEMOGLOBIN AND MYOGLOBIN: O2-BINDING PROTEINS
CHEMISTRY OF HAEMOGLOBIN AND HAEMOGLOBINOPATHIES
HAEMOGLOBIN
STRUCTURE OF HB
VARIETIES OF NORMAL HUMAN HAEMOGLOBIN
DERIVATIVES OF HAEMOGLOBIN
COMBINATION OF HAEMOGLOBIN WITH GASES
ABNORMAL HAEMOGLOBINS AND HAEMOGLOBINOPATHIES
ABNORMAL HAEMOGLOBINS
HAEMOGLOBINOPATHIES
ABNORMAL HAEMOGLOBINS WHICH PRODUCE METHAEMOGLOBINEMIA
ABNORMAL HAEMOGLOBINS ASSOCIATED WITH HIGH O2-AFFINITY
ABNORMAL HB WHICH INTERFERES WITH M-RNA FORMATION
THALASSAEMIAS

CHEMISTRY OF RESPIRATION AND FREE RADICALS
TRANSPORT OF OXYGEN
CLINICAL IMPORTANCE OF OXYGEN
TRANSPORT OF CARBON DIOXIDE
FREE RADICALS

COLLAGEN: PROTOTYPICAL FIBROUS PROTEIN

TOC
LIPIDS - CHEMISTRY & STRUCTURE
(Hecketsweiler, Lipides Formules) V1 JPG 1 - V1 JPG 2
(Kamoun, Lipides Structure) V1 PDF

LIPIDS
CLASSIFICATION OF LIPIDS
DERIVED LIPIDS
ESSENTIAL FATTY ACIDS
ALCOHOLS
CHOLESTEROL
OTHER STEROLS OF BIOLOGICAL IMPORTANCE 52 •
SIMPLE LIPIDS
IDENTIFICATION OF FATS AND OILS
COMPOUND LIPIDS
GLYCOLIPIDS

PROSTAGLANDINS
METABOLISM OF PROSTAGLANDINS
FUNCTIONS OF PROSTAGLANDINS
CHEMISTRY AND FUNCTIONS OF PROSTACYCLINS AND THROMBOXANES
LEUCOTRIENES-LTS
LIPOXINS

OVERVIEW
FATTY ACIDS
(TRI) ACYLGLYCEROLS & DERIVATIVES
WAXES
GLYCERO - PHOSPHOLIPIDS
PLASMALOGENS
SPHINGO - LIPIDS
STEROIDS
EICOSANOIDS
LIPOPROTEINS

TOC
NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS - CHEMISTRY & STRUCTURE
Primary Secondary Tertiary Quaternary Determination Prediction Design Thermodynamics
Structural motif Nucleic acid double helix

TYPES OF NUCLEIC ACIDS
CONSTITUENTS
Nucleobases - Nucleosides - Nucleotides - Deoxynucleotides
RIBONUCLEIC ACIDS (CODING, NON-CODING)
Translational   
Messenger (precursor, heterogenous nuclear) -  modified Messenger - Transfer - Ribosomal - Transfer-messenger
Regulatory   
Interferential (Micro Small interfering Piwi-interacting) - Antisense - Processual (Small nuclear Small nucleolar Small Cajal Body RNAs Y RNA) - Enhancer RNAs
Others   
Guide - Ribozyme - Small hairpin - Small temporal - Trans-acting small interfering - Subgenomic messenger
DEOXYRIBONUCLEIC ACIDS
Organellar (Chloroplast Mitochondrial) - Complementary - Deoxyribozyme- Genomic - Hachimoji- Multicopy single-stranded
ANALOGUES
Xeno (Glycol Threose Hexose) - Locked - Peptide - Morpholino
CLONING VECTORS   
Phagemid - Plasmid - Lambda phage - Cosmid - Fosmid - Artificial chromosomes (P1-derived Bacterial Yeast Human)

TOC
ENERGY - CHEMISTRY & STRUCTURE
(Hecketsweiler, Energies Formules) V1 JPG 1 - V1 JPG 2

PHYSICO-CHEMICAL ASPECTS OF BIOCHEMICAL PROCESSESS
Energetics of Chemical Reactions
Redox Reactions
Transport Through Membranes
Uncharged molecules
Charged molecules
Enzyme Kinetics
Velocity of reactions
Enzyme catalyzed one-substrate reaction
Michaelis constant
Characterization of enzyme activities
Inhibition
Two-substrate reactions
Dependence of reactions on temperature and activation energy
Fractal enzyme kinetics

TOC
CELLULAR

CLASSIFICATION OF LIVING ORGANISMS

TYPE OF CELLS

STRUCTURE OF CELLS
PROKARYOTIC CELLS
GENERAL CHARACTERISTICS OF EUKARYOTIC CELLS
Nucleus
Cytosol
Endoplasmic reticulum
Golgi apparatus
Lysosomes
Peroxisomes
Mitochondria
Cytoskeleton
SPECIAL STRUCTURES OF PLANT CELLS
Plant cell walls
Chloroplasts
Vacuoles
SPECIAL STRUCTURES OF ANIMAL CELLS
Animal cell membrane and extracellular matrix
Interconnection between cells

PROTEIN STRUCTURE & FUNCTION

LEVELS OF ORGANIZATION
Primary structure
Secondary structure
α-Helix
β-Pleated sheet
Tertiary structure
Quaternary structure
Globular proteins
Fibrous proteins
α-Keratin
Collagen

PROTEIN FUNCTION
Enzyme catalysis
Transport
Storage
Motion
Structural and mechanical support
Defense
Signal transduction
Control of growth, differentiation and metabolism
Toxin
Membrane Proteins
Peripheral Membrane Proteins
Transmembrane Proteins
Transport Proteins
Carrier Proteins (Transporters)
Channel Proteins (Ion Channels)
G-Protein Coupled Receptors
Gs- and Gi-Protein Signaling
GQ-Protein Signaling

ENZYMES

NUCLEIC ACID STRUCTURE
COMPONENTS OF NUCLEIC ACID
PROPERTIES OF RNA CHAINS
PROPERTIES OF DNA CHAINS
COMPACTION LEVELS OF DNA CHAINS
Bacterial genomes
Eukaryotic genomes
Organization levels
Mitosis

GENETIC CODE & FLOW OF INFORMATION
From DNA to RNA
From Nucleic Acids to Proteins – The Genetic Code
Influence of Errors

POLYMERIC CARBOHYDRATES
Polymeric Carbohydrates in Energy Storage
Starch
Glycogen
Polymeric Carbohydrates as Structural Elements
Cellulose
Chitin

GLYCOSYLATED PROTEINS & PEPTIDES
Glycoproteins
Proteoglycans
Degradation Diseases and Mucopolysaccharidoses
Repeating Units of Glycosaminoglycans as Components of Proteoglycans
Peptidoglycans

LIPID AGGREGATES & MEMBRANES - BIOLOGICAL MEMBRANES
Characteristics of membranes
Lipoproteins
Mitochondrial Membranes
Chemical Composition of the Membranes
Functions: Transport System

CELL CYCLE PHASES
Regulation of cell cycle
Cyclin-dependent kinases
Cyclin-CDK complexes
Tumor suppressors
Cell types
Permanent
Stable (quiescent)
Labile

ROUGH ENDOPLASMIC RETICULUM

SMOOTH ENDOPLASMIC RETICULUM

CELL TRAFFICKING
I-cell disease
Signal recognition particle (SRP)
Vesicular trafficking proteins

PEROXISOME
Zellweger syndrome
Refsum disease
Adrenoleukodystrophy

PROTEASOME

CYTOSKELETAL ELEMENTS
Microfilaments
Intermediate filaments
Microtubules

MICROTUBULE
Molecular motor proteins

CILIA STRUCTURE

PRIMARY CILIARY DYSKINESIA

SODIUM-POTASSIUM PUMP

COLLAGEN
COLLAGEN SYNTHESIS AND STRUCTURE
OSTEOGENESIS IMPERFECTA
EHLERS-DANLOS SYNDROME
MENKES DISEASE
ELASTIN

TOC
METABOLISM & HOMEOSTASIS

TOC
ACID - BASE RELATIONSHIPS
ACIDIC DISSOCIATION
MEASURES OF ACIDITY
BUFFERS
ACID–BASE BALANCE
ACID–BASE DISORDERS
CLINICAL RELEVANCE: DIABETIC KETOACIDOSIS

TOC
OVERVIEW OF METABOLISM - SUMMARY OF PATHWAYS
(Gerhard, General Metabolism) V1 JPG
(Gerhard, Cellular Communication & Protein Biosynthesis) V1 JPG
(Ferrier, Important Reactions of Intermediary Metabolism) V1 JPG
(Hecketsweiler, Grandes Voies Métaboliques & Nutrition )  V1 JPG
(Hecketsweiler, Panorama) V1 PDF
(Hecketsweiler, Destin des aliments) V1 JPG
(Hecketsweiler, Période alimentaire Rapport Insuline/Glucagon Elevé) V1 JPG
(Hecketsweiler, Situation de jeune Rapport Insuline/Glucagon Bas) V1 JPG
(Hecketsweiler, Enzymes, Régulations, Spécificités tissulaires) V1 JPG
(Hecketsweiler, Aperçu des anomalies métaboliques)  V1 JPG 1 - V1 JPG 2

CATABOLISM
CLASSIFICATION OF ORGANISMS BASED ON THEIR METABOLISM
DIGESTION FROM ORGANIC COMPOUNDS
ENERGY FROM ORGANIC COMPOUNDS

ENERGY TRANSFORMATIONS
OXIDATIVE PHOSPHORYLATION
ENERGY FROM INORGANIC COMPOUNDS
ENERGY FROM LIGHT

ANABOLISM
CARBON FIXATION
CARBOHYDRATES & GLYCANS
FATTY ACIDS, ISOPRENOIDS & STEROL
PROTEINS
NUCLEOTIDE SYNTHESIS & SALVAGE

XENOBIOTICS & REDOX METABOLISM
THERMODYNAMICS OF LIVING ORGANISMS
REGULATION & CONTROL
EVOLUTION
INVESTIGATION & MANIPULATION
HISTORY

GENERAL
Metabolic pathway
Metabolic network
Primary nutritional groups

METABOLISM SITES
Mitochondria
Cytoplasm
Both

ATP PRODUCTION
Aerobic metabolism
Anaerobic glycolysis

ACTIVATED CARRIERS
ATP
NADH, NADPH, FADH2
CoA, lipoamide
Biotin
Tetrahydrofolates
S-adenosylmethionine (SAM)
TPP

UNIVERSAL ELECTRON ACCEPTORS
Nicotinamides (NAD+, NADP+ from vitamin B3) and flavin nucleotides (FAD from vitamin B2)

REGULATION

TOC
ENZYMES - PROTEIN CATALYSTS
Accelerate the rate of reactions
Substrate specificity
Reaction specificity

CHEMISTRY OF ENZYMES
NOMENCLATURE AND CLASSIFICATION OF ENZYMES
SPECIFICITY OF ENZYMES
MECHANISM OF ENZYME ACTION
MODELS OF ENZYME-SUBSTRATE COMPLEX FORMATION
KINETIC PROPERTIES OF ENZYMES
FACTORS AFFECTING ENZYME ACTION
ENZYME INHIBITION

OVERVIEW
GENERAL PROPERTIES OF ENZYMES
COENZYMES AND PROSTHETIC GROUPS
ACTIVE SITE
ENZYME KINETICS
ENZYME INHIBITION
COOPERATIVITY AND ALLOSTERISM
CELLULAR STRATEGIES FOR REGULATING METABOLIC PATHWAYS

ENERGY RELATIONSHIPS
FREE-ENERGY CHANGE
ENZYMES AS BIOLOGICAL CATALYSTS
MICHAELIS-MENTEN EQUATION
LINEWEAVER-BURK EQUATION
ENZYME REGULATION
CLINICAL RELEVANCE: METHANOL & ETHYLENE GLYCOL POISONING

GENERAL
Nomenclature
Activity
Thermodynamics
Gibbs Free Energy Change
The Equilibrium Constant
KINETICS

CATALYTIC MECHANISM
Single-substrate reaction
Two-substrate reactions
Catalytic center
Typical catalytic mechanisms
Cofactors
Coenzymes
Prosthetic groups
Effects of pH
Effects of temperature
ISOENZYMES
MULTIENZYME COMPLEXES
REACTION RATE
CLASSIFICATION OF ENZYMES
1. Oxidoreductases
2. Transferases
3. Hydrolases
4. Lyases
5. Isomerases
6. Ligases
ENZYME TERMINOLOGY
Kinase
Phosphorylase
Phosphatase
Dehydrogenase
Hydroxylase
Carboxylase
Mutase
Synthase/synthetase

REGULATION OF THE ENZYME ACTIVITY
REGULATION OF THE QUANTITY OF ENZYMES
Regulation of enzyme synthesis and degradation
Zymogen activation
REGULATION OF THE ACTIVITY OF ENZYMES
Regulation depending on substrate concentration
Competitive inhibition
Noncompetitive inhibition
Uncompetitive inhibition
Allosteric regulation
Covalent modification
Cascade mechanisms
SITE OF REGULATION
REGULATION
pH
Temperature
Concentration
Covalent Modification
Phosphorylation and Dephosphorylation
Zymogens (Proenzymes)
Allosteric Regulation

RATE-DETERMINING ENZYMES OF METABOLIC PROCESSES
Glycolysis Phosphofructokinase-1 (PFK-1)
Gluconeogenesis Fructose-1,6-bisphosphatase 1
TCA cycle Isocitrate dehydrogenase
Glycogenesis Glycogen synthase
Glycogenolysis Glycogen phosphorylase
HMP shunt Glucose-6-phosphate dehydrogenase (G6PD)
De novo pyrimidine synthesis Carbamoyl phosphate synthetase II
De novo purine synthesis Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
Urea cycle Carbamoyl phosphate synthetase I
Fatty acid synthesis Acetyl-CoA carboxylase (ACC)
Fatty acid oxidation Carnitine acyltransferase I
Ketogenesis HMG-CoA synthase
Cholesterol synthesis HMG-CoA reductase

TOC
ENERGY METABOLISM - GENERATION OF ENERGY FROM DIETARY FUELS

AEROBIC RESPIRATION   
Glycolysis → Pyruvate decarboxylation → Citric acid cycle → Oxidative phosphorylation (electron transport chain + ATP synthase)
ANAEROBIC RESPIRATION   
Electron acceptors other than oxygen
FERMENTATION   
Glycolysis → Substrate-level phosphorylation (ABE Ethanol Lactic acid)

BIOLOGICAL OXIDATION
REDOX POTENTIAL AND FREE ENERGY
MITOCHONDRIAL ELECTRON TRANSPORT CHAIN
DETAIL STRUCTURE AND FUNCTIONS OF ELECTRON TRANSPORT CHAIN (ETC)
INHIBITORS OF ELECTRON TRANSPORT CHAIN
OXIDATIVE PHOSPHORYLATION
UNCOUPLERS OF OXIDATIVE PHOSPHORYLATION

CITRIC ACID CYCLE, ELECTRON TRANSFER REACTIONS & OXIDATIVE PHOSPHORYLATION - ELECTRON TRANSPORT CHAIN
(Hecketsweiler, Résumé du catabolisme énergétique) V1 JPG

ENERGETICS OF METABOLIC PATHWAYS
Overview
Change in free energy (deltaG)
Coupled reactions
ATP-ADP cycle
Redox coenzymes
CELLULAR ENERGY & ADENOSINE TRIPHOSPHATE
COUPLED CHEMICAL REACTIONS PROVIDE THE ENERGY NEEDED FOR CELLULAR WORK
HIGH-ENERGY PHOSPHATE COMPOUNDS

INTRODUCTION TO INTERMEDIARY METABOLISM
Overview
Catabolic stages
Compartmentation of metabolic pathways
Five common perspectives for many metabolic pathways

PYRUVATE TURNOVER & ACETYL-COENZYME A
Pyruvate Oxidation
Regulation of Pyruvate Dehydrogenase Activity
Acetyl-Coenzyme A
Anaplerotic Reactions
Pyruvate carboxylase
‘Malic enzyme’
Phosphoenolpyruvate carboxykinase
Phosphoenolpyruvate carboxylase reaction
Initiation of Gluconeogenesis
Alcoholic Fermentation

xxx
TCA (KREBS) CYCLE - CITRATE CYCLE - CITRIC ACID CYCLE (CAC)
OVERVIEW
REACTION SEQUENCE
PATHWAY REACTION STEPS
FUNCTION
Production of high-energy electron carriers for ATP generation in mitochondria
LOCATION
Mitochondria
REACTANTS
Pyruvate and acetyl-CoA derived from protein and fat breakdown
PRODUCTS
3 NADH, 1 FADH2, 2 CO2, 1 GTP. All equivalent to 12 ATP per acetyl-CoA
CYCLE
REGULATION - REGULATED STEPS
ENERGY BALANCE
UNIQUE CHARACTERISTICS
INTERFACE WITH OTHER PATHWAYS
CLINICAL RELEVANCE
xxx
PRODUCTS OF THE CITRIC ACID CYCLE (ONE REVOLUTION)
xxx
SYNTHETIC FUNCTION OF THE CITRIC ACID CYCLE
INTERMEDIATES
ANAPLEROTIC REACTIONS
xxx
REGULATION OF THE CITRIC ACID CYCLE
ACETYL COA
ISOCITRATE
ALPHA-KETOGLUTARATE
xxx

xxx
ELECTRON TRANSPORT & OXIDATIVE PHOSPHORYLATION
OVERVIEW
ELECTRON TRANSPORT CHAIN ETC
OXIDATIVE PHOSPHORYLATION
ATP SYNTHASE AND CHEMIOSMOTIC COUPLING
RESPIRATORY CONTROL
MITOCHONDRIAL DNA MUTATIONS

MITOCHONDRIAL TRANSPORT SYSTEMS
OVERVIEW
ATP-ADP TRANSLOCASE
NADH SHUTTLE MECHANISMS
SPECIALIZED INNER MEMBRANE TRANSPORTERS

INHIBITORS OF MITOCHONDRIAL ATP SYNTHESIS
OVERVIEW
ELECTRON-TRANSPORT BLOCKERS
UNCOUPLERS
MITOCHONDRIAL MALFUNCTION

ELECTRON TRANSPORT & OXIDATIVE PHOSPHORYLATION
THE OXIDATION–REDUCTION POTENTIAL
OXIDATIVE PHOSPHORYLATION

CHEMIOSMOTIC HYPOTHESIS
RESPIRATORY COMPLEXES AS PROTON PUMPS
ATP SYNTHASE COMPLEX (COMPLEX V)

CLINICAL RELEVANCE
UNCOUPLING AGENTS
INHIBITORS

GENERAL PRINCIPLES
DIFFERENT TYPES OF ELECTRON TRANSPORT CHAINS
THE ENERGETIC BASIS OF THE OXIDATIVE PHOSPHORYLATION
ELECTRON TRANSPORT SYSTEM IN MITOCHONDRIA & BACTERIA
Complex I: NADH:Ubiquinone Oxidoreductase
Complex II: Succinate:Ubiquinone Oxidoreductase
Complex III: Ubiquinol: Cytotochrome-c Reductase
Complex IV: Ferrocytochrome-c: Oxygen Oxidoreductase
Complex V: ATP Synthase
FUNCTION
Transduction of high-energy e– from NADH and FADH2 to ATP
LOCATION
Mitochondria
REACTANTS
NADH, FADH2, and O2 as the final electron acceptor
Glycerol phosphate shuttle
Malate-aspartate shuttle
PRODUCTS
ATP and H2O
ATP produced via ATP synthase
1 NADH > 2.5 ATP; 1 FADH2 > 1.5 ATP
CYCLE
OXIDATIVE PHOSPHORYLATION POISONS
Electron transport inhibitors
ATP synthase inhibitors
Uncoupling agents

TOC
CARBOHYDRATE METABOLISM
(Hecketsweiler, Glucides Résumé Métabolisme) V1 JPG

HUMAN
Glycolysis ⇄ Gluconeogenesis
Glycogenolysis ⇄ Glycogenesis
Pentose phosphate pathway - Fructolysis (Polyol pathway) - Galactolysis (Leloir pathway)
Glycosylation (N-linked O-linked)
NONHUMAN
Photosynthesis - Anoxygenic photosynthesis - Chemosynthesis - Carbon fixation
DeLey-Doudoroff pathway - Entner-Doudoroff pathway
Xylose metabolism - Radiotrophism

AEROBIC RESPIRATION : GLYCOLYSIS → PYRUVATE DECARBOXYLATION → CITRIC-ATE ACID = TCA (KREBS) CYCLE → OXIDATIVE PHOSPHORYLATION (ELECTRON TRANSPORT CHAIN + ATP SYNTHASE)

CARBOHYDRATE DIGESTION & ABSORPTION
DIETARY
DI-SACCHARIDES OLIGO POLY
MONO-SACCHARIDES
Oxidation to CO2 and H2O for energy
Storage as glycogen
Conversion to triglyceride (fat)
Release into the general circulation (as glucose)

REGULATION OF GLYCOLYSIS & GLUCONEOGENESIS
This is accomplished by control of the magnitude and direction of flow at two steps
During starvation
In the fed (absorptive) state

CLINICAL RELEVANCE
Glycogen storage diseases are inherited enzyme deficiencies
Hereditary enzyme deficiencies in sucrose metabolism
Inherited enzyme deficiencies in lactose metabolism

GLYCOLYSIS & THE FATE OF PYRUVATE
glucose to pyruvate
cytosol
anaerobic
aerobic
first step
first phase
second phase
NADH generated
OVERVIEW
FUNCTION
Breakdown of glucose into pyruvate, which either proceeds to lactate (anaerobic glycolysis) or the Krebs (TCA) cycle (aerobic glycolysis)
Supplies energy
Supplies reducing equivalents
Converts carbohydrates
Substrate channeling
GLUCOSE
Mannose
Galactose
FRUCTOSE
SORBITOL
LOCATION
Cytoplasm of cells that use glucose
GLYCOLYSIS AND PYRUVATE OXIDATION: PATHWAY REACTION STEPS
REACTANTS
Glucose
PRODUCTS
2 Pyruvate, 2 ATP, & 2 NADH
Aerobic
Anaerobic
CYCLE
REGULATION - GLYCOLYSIS AND PYRUVATE OXIDATION: REGULATED STEPS
Key enzymes
Require ATP
Hexokinase Glucokinase Hexokinase vs glucokinase
Phosphofructokinase 1 (PFK-1)
Produce ATP
Phosphoglycerate kinase Pyruvate kinase
Regulation by fructose-2,6-bisphosphate
REGULATION STEPS IN GLYCOLYSIS
Phosphorylation Hexokinase Glucokinase
Dephosphorylation Committing step Pasteur-effect Pyruvate kinase
Induction of enzymes
GLYCOLYSIS AND PYRUVATE OXIDATION: UNIQUE CHARACTERISTICS
GLYCOLYSIS AND PYRUVATE OXIDATION: INTERFACE WITH OTHER PATHWAYS
PATHOPHYSIOLOGY - GLYCOLYSIS AND PYRUVATE OXIDATION: CLINICAL RELEVANCE
RESORPTION OF GLUCOSE
RESPONSE OF ANIMAL ORGANS TO HIGH & LOW GLUCOSE LEVELS
Effects after glucose intake
Effects of starvation or sudden energy demand

DI- & OLIGOSACCHARIDES - SUCROSE & LACTOSE METABOLISM
SUCROSE
LACTOSE
OTHER GLYCOSIDES

METABOLISM OF HEXOSE DERIVATIVES
URONIC ACIDS
ALDONIC ACIDS
ALDONIC ACIDS
INOSITOL
HEXITOLS
MANNOSE & DEOXY HEXOSES

PENTOSE METABOLISM
PENTOSE PHOSPHATE CYCLE
OTHER DECARBOXYLATION REACTIONS
PLANT CELL WALLS
Cell wall synthesis
Degradation of wood
PENTOSE METABOLISM IN HUMANS

PENTOSE PHOSPHATE PATHWAY (HMP SHUNT)
This pathway may function as an alternate form of glycolysis, or it may be the route for the complete oxidation of glucose (it begins with glucose 6-phosphate)
irreversible oxidative portion generates NADPH
RIBOSE 5-PHOSPHATE, needed for nucleotide synthesis
OVERVIEW
PENTOSE PHOSPHATE PATHWAY: PATHWAY REACTION STEPS
PENTOSE PHOSPHATE PATHWAY: REGULATED STEPS
PENTOSE PHOSPHATE PATHWAY: UNIQUE CHARACTERISTICS
PENTOSE PHOSPHATE PATHWAY: INTERFACE WITH OTHER PATHWAYS
PENTOSE PHOSPHATE PATHWAY: CLINICAL RELEVANCE
FUNCTION
1. Shunts G6P to form ribulose-5—for nucleotide synthesis.
2. Generation of NADPH for: - Regeneration of GSH in the GSH/GSSG antioxidant system - Steroid and fatty acid biosynthesis
LOCATION
Cytoplasm
REACTANTS
G6P
PRODUCTS
Ribulose-5-phosphate, NADPH, and CO2
CYCLE
REGULATION
PATHOPHYSIOLOGY
REACTIONS
Oxidative (irreversible)
Nonoxidative (reversible)
GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFCIENCY

AMINO SUGARS
BIOSYNTHESIS
CATABOLISM

Pyruvate Dehydrogenase Complex
Mitochondrial enzyme complex linking glycolysis and TCA cycle
Pyruvate dehydrogenase complex deficiency
Pyruvate metabolism

PYRUVATE TURNOVER & ACETYL-COENZYME A
Pyruvate Oxidation
Regulation of Pyruvate Dehydrogenase Activity
Acetyl-Coenzyme A
Anaplerotic Reactions
Pyruvate carboxylase
‘Malic enzyme’
Phosphoenolpyruvate carboxykinase
Phosphoenolpyruvate carboxylase reaction
Initiation of Gluconeogenesis
Alcoholic Fermentation

TCA (KREBS) CYCLE - CITRATE CYCLE
Reaction Sequence
Function
Production of high-energy electron carriers for ATP generation in mitochondria
Location
Mitochondria
Reactants
Pyruvate and acetyl-CoA derived from protein and fat breakdown
Products
3 NADH, 1 FADH2, 2 CO2, 1 GTP. All equivalent to 12 ATP per acetyl-CoA
Cycle
Regulation
Energy Balance

GLYOXYLATE METABOLISM
Glyoxylate Cycle
Other Glyoxylate Reactions

METABOLISM OF GALACTOSE AND FRUCTOSE
OVERVIEW
GALACTOSE METABOLISM: PATHWAY REACTION STEPS
GALACTOSE METABOLISM: REGULATED STEPS
GALACTOSE METABOLISM: UNIQUE CHARACTERISTICS
GALACTOSE METABOLISM: INTERFACE WITH OTHER PATHWAYS
GALACTOSE METABOLISM: CLINICAL RELEVANCE
FRUCTOSE METABOLISM: PATHWAY REACTION STEPS
FRUCTOSE METABOLISM: REGULATED STEPS
FRUCTOSE METABOLISM: UNIQUE CHARACTERISTICS
FRUCTOSE METABOLISM: INTERFACE WITH OTHER PATHWAYS
FRUCTOSE METABOLISM: CLINICAL RELEVANCE

FRUCTOSE METABOLISM
Function
Converts fructose to substrate for glycolysis
Location
Muscle, kidney, and liver
Reactants
Fructose
Products
Glyceraldehyde-3- phosphate
Cycle
Pathophysiology
Essential fructosuria
Hereditary fructose intolerance

GALACTOSE METABOLISM
Function
Converts galactose to substrate for glycolysis
Location
Kidney, liver, and brain
Reactants
Galactose and ATP
Products
Glucose-1-phosphate
Cycle
Pathophysiology
Galactokinase deficiency
Classic galactosemia

Sorbitol
Lactase defciency

ANAEROBIC METABOLISM & CORI CYCLE
Function
Cori cycle shuttles lactate from anaerobic metabolism in muscle to liver
Location
Shuttles lactate from muscle to liver
Reactants
Lactate and 6 ATP
Products
Glucose
Cycle

Transport of ammonia by alanine
Hyperammonemia

GLUCONEOGENESIS
This process carries out the synthesis of glucose from small noncarbohydrate precursors such as lactate and alanine
liver and kidney
reversible reactions of glycolysis
bypass the nonreversible
brain and exercising muscle
Gluconeogenic substrates
Cori cycle
OVERVIEW
GLUCONEOGENESIS: PATHWAY REACTION STEPS
GLUCONEOGENESIS: REGULATED STEPS
GLUCONEOGENESIS: UNIQUE CHARACTERISTICS
GLUCONEOGENESIS: INTERFACE WITH OTHER PATHWAYS
GLUCONEOGENESIS: CLINICAL RELEVANCE
FUNCTION
Generates glucose from glycolysis intermediates, fatty acid or TCA cycle
LOCATION
Cytoplasm and mitochondria of kidney and liver, intestinal epithelium
REACTANTS
All substrates end up as pyruvate/phosphoenolpyruvate →conversion to glucose
PRODUCTS
Glucose
CYCLE
REGULATION
GLUCONEOGENESIS, IRREVERSIBLE ENZYMES
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose-1,6-bisphosphatase 1
Glucose-6-phosphatase

POLYSACCHARIDE METABOLISM
Important Polysaccharides
Glycogen Starch
Cellulose
Fructans
Dextran
Biosynthesis of Polysaccharides
Glycogen synthesis
Starch synthesis
Cellulose synthesis
The synthesis of dextrans and fructans
Catabolism of Polysaccharides
Animal glycogen degradation
The degradation of starch
Cellulose

GLYCOGEN METABOLISM
storage form
OVERVIEW
GLYCOGEN METABOLISM: PATHWAY REACTION STEPS
GLYCOGEN METABOLISM: REGULATED STEPS
GLYCOGEN METABOLISM: UNIQUE CHARACTERISTICS
GLYCOGEN METABOLISM: INTERFACE WITH OTHER PATHWAYS
GLYCOGEN METABOLISM: CLINICAL RELEVANCE
FUNCTION
Maintains glucose homeostasis
LOCATION
Glycogenesis (muscle and liver), glycogenolysis (heart, muscle, and liver)
REACTANTS
Glycogen/glucose
PRODUCTS
Glycogen/glucose
GLYCOGENESIS
GLYCOGENOLYSIS
REGULATION
REGULATION OF GLYCOGEN METABOLISM IN MAMMALS
Phosphorylation
Dephosphorylation
Allosteric mechanisms
GLYCOGEN REGULATION BY INSULIN & GLUCAGON/EPINEPHRINE
PATHOPHYSIOLOGY
GLYCOGEN
Skeletal muscle
Hepatocytes
GLYCOGEN STORAGE DISEASES - MEDICAL ASPECTS
Von Gierke disease (type I)
Pompe disease (type II)
Cori disease (type III)
Andersen disease (type IV)
McArdle disease (type V)

LYSOSOMAL STORAGE DISEASES
Sphingolipidoses
Tay-Sachs disease
Fabry disease
Metachromatic leukodystrophy
Krabbe disease
Gaucher disease
Niemann-Pick disease
Mucopolysaccharidoses
Hurler syndrome
Hunter syndrome

GLYCOPROTEINS & PROTEOGLYCANS
OVERVIEW
GLYCOPROTEINS
PROTEOGLYCANS

TOC
LIPID METABOLISM & GLYCOLIPIDS
(Hecketsweiler, Lipides Résumé Métabolisme) V1 JPG

OTHER
STEROID METABOLISM
SPHINGOLIPID METABOLISM
EICOSANOID METABOLISM
KETOSIS
REVERSE CHOLESTEROL TRANSPORT

LIPID FUNCTION
FAT
PHOSPHOLIPIDS
SPHINGOLIPIDS
CHOLESTEROL

LIPID DIGESTION
water insoluble - emulsified
mouth - stomach
lingual lipase - gastric lipase
triacylglycerols -  diacylglycerols - short-chain & medium-chain fatty acids -  phospholipids - cholesterol esters
duodenum
emulsified - bile salts
small intestine
hydrolyzed - pancreatic lipase
phospholipase A
cholesterol esterase
micelles - absorbed - small intestine
Medium-chain TGs - hydrolyzed
Medium-chain fatty acids (MCFAs, 8 to 10 carbons) - portal vein blood
Long-chain fatty acids (LCFAs, sup 12 carbons) - reincorporated into TG
TGs - incorporated into chylomicrons - lymphatics - enter the circulation via the thoracic duct

PLASMA LIPOPROTEINS
OVERVIEW
STRUCTURE AND COMPOSITION OF LIPOPROTEINS
FUNCTIONS AND METABOLISM OF LIPOPROTEINS
HEREDITARY DISORDERS RELATED TO DEFECTIVE LIPOPROTEIN METABOLISM

LIPOPROTEIN TRANSPORT & METABOLISM
core - triacylglycerols & cholesterol esters
outer layer - cholesterol, phospholipids & apoproteins
EXOGENOUS LIPID (from the intestine)
Chylomicrons
Chylomicron TG
FFAs & glycerol - lipoprotein lipase - muscle & adipose tissue
chylomicron remnants
receptor-mediated endocytosis
SOME FFAs
serum albumin - nonesterified fatty acids
hormone-sensitive lipase - glucagon & epinephrine
ENDOGENOUS LIPID (from the liver)
very-low-density lipoprotein
VLDL triglyceride
lipoprotein lipase - low-density lipoproteins
LDLs
LDL receptors - liver
HMG coenzyme A (CoA) reductase
LDL receptor synthesis
High-density lipoproteins
reverse cholesterol transport
ABCA1
SRB1
cholesterol esters - cholesterol ester transfer protein (CETP) - receptor-mediated endocytosis

TRIACYLGLYCEROL MOBILIZATION AND FATTY ACID OXIDATION
OVERVIEW
TRIACYLGLYCEROL MOBILIZATION AND FATTY ACID OXIDATION: PATHWAY REACTION STEPS
TRIACYLGLYCEROL MOBILIZATION AND FATTY ACID OXIDATION: REGULATED STEPS
TRIACYLGLYCEROL MOBILIZATION AND FATTY ACID OXIDATION: UNIQUE CHARACTERISTICS
TRIACYLGLYCEROL MOBILIZATION AND FATTY ACID OXIDATION: INTERFACE WITH OTHER PATHWAYS
TRIACYLGLYCEROL MOBILIZATION AND FATTY ACID OXIDATION: CLINICAL RELEVANCE

OXIDATION OF FATTY ACIDS - DEGRADATION
MITOCHONDRIAL MATRIX
CARNITINE
BETA-OXIDATION SYSTEM
odd-numbered fatty acids - propionyl CoA
succinyl CoA - biotin and vitamin B12
gluconeogenesis
KETOGENESIS
acetoacetate - beta-hydroxybutyrate - liver
hydroxymethylglutaryl CoA
acetoacetate
beta-hydroxybutyrate - acetone
Extrahepatic tissues
The glucose-starved brain

FATTY ACID AND TRIACYLGLYCEROL SYNTHESIS
OVERVIEW
FATTY ACID AND TRIACYLGLYCEROL SYNTHESIS: PATHWAY REACTION STEPS
FATTY ACID AND TRIACYLGLYCEROL SYNTHESIS: REGULATED STEPS
FATTY ACID AND TRIACYLGLYCEROL SYNTHESIS: UNIQUE CHARACTERISTICS
FATTY ACID SYNTHESIS: INTERFACE WITH OTHER PATHWAYS
FATTY ACID AND TRIACYLGLYCEROL SYNTHESIS: CLINICAL RELEVANCE

FATTY ACID SYNTHESIS
FATTY ACID SYNTHASE
primary substrates - acetyl CoA - malonyl CoA
ACETYL COA
pyruvate dehydrogenase
citrate-malate-pyruvate shuttle
NADPH - pentose phosphate pathway
MALONYL COA
ACETYL AND MALONYL MOIETIES
sulfhydryl groups in the fatty acid synthase
final products, palmitate and fatty acid synthase
PALMITATE
essential fatty acids - Lineoleic acid and linolenic acid
eicosanoid cascade - leukotrienes, eicosanoates, prostaglandins, and thromboxanes

GLYCEROLIPID SYNTHESIS
liver, adipose tissue, and the intestine
glycerol 3-phosphate
phosphatidate
Triacylglycerol - acyl group from acyl CoA
Phosphatidyl choline - phosphatidyl ethanolamine - cytidine diphosphate (CDP) derivative
Phosphatidylserine
Phosphatidylinositol - CDP-diacylglycerol

SPHINGOLIPID SYNTHESIS
palmityl CoA and serine - dihydrosphingosine and sphingosine
ceramide

CHOLESTEROL SYNTHESIS
liver and intestinal mucosa from acetyl CoA
key intermediate - HMG CoA
HMG CoA reductase
terpenes vitamin A, vitamin K, coenzyme Q
steroid hormones in the adrenal cortex, ovaries, placenta, and testes
bile acids
7-DEHYDROCHOLESTEROL - vitamin D

CLINICAL RELEVANCE
LIPID MALABSORPTION
HYPERLIPIDEMIAS
CLINICAL EXPRESSION OF DISRUPTIONS IN FATTY ACID OXIDATION
SPHINGOLIPIDOSES

FATTY ACIDS & ACYL-COA
BIOSYNTHESIS OF FATTY ACIDS
Reaction sequence
Biosynthesis of fatty acids of medium chain length
Biosynthesis of odd-numbered & branched fatty acids
REGULATION OF FATTY ACID SYNTHESIS
FATTY ACID DESATURATION & CHAIN ELONGATION
Desaturation
Importance of unsaturated fatty acids
Elongation
TRANSPORT & ACTIVATION OF FATTY ACIDS
Fatty acids are transported
Activation of fatty acids
Degradation
FATTY ACID OXIDATION
Beta-Oxidation in animals
Medical aspects of fatty acid oxidation
Regulation of fatty acid oxidation in mammals
Initiation of fatty acid degradation by an oxidase reaction
Fatty acid oxidation in plants
The fatty acid oxidation in E. coli
ENERGY YIELD OF THE FATTY ACID OXIDATION
KETONE BODIES
SYSTEMIC 1° CARNITINE DEFICIENCY
MEDIUM-CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY

TRIACYLGLYCEROLS (TRIGLYCERIDES)
Biosynthesis of Triacylglycerols (Lipogenesis)
Regulation of triacylglycerol synthesis
Mobilization of Triacylglycerols (Lipolysis)

PHOSPHOLIPIDS
Occurrence of Phospholipids
Glycerophospholipids (Phosphoglycerides)
Biosynthesis
Bacteria
Animals, plants and yeast
Remodelling of fatty acid substituents
Degradation of glycerophospholipids
Metabolic role of glycerophospholipids and phospholipases
Ether Lipids
Biosynthesis
Sphingophospholipids
Biosynthesis
Choline, Betaine, Sarcosine
Choline metabolism
Betaine metabolism
Biosynthesis
Osmoprotection
Sarcosine metabolism
Sarcosine synthesis from glycine

SPHINGOLIPID DEGRADATION
OVERVIEW
CERAMIDE
SPHINGOLIPID DEGRADATION
SPHINGOLIPIDOSES

GLYCOLIPIDS
GLYCOSPHINGOLIPIDS
Gangliosides
Biosynthesis
Degradation
Medical aspects
GLYCOGLYCEROLIPIDS
Biosynthesis and biodegradation
Biodegradation
GLYCOSYLPHOSPHOPOLYPRENOLS

TOC
STEROIDS & ISOPRENOIDS

CHOLESTEROL AND STEROID METABOLISM
OVERVIEW
CHOLESTEROL SYNTHESIS AND REGULATION
BILE SALTS AND BILE ACIDS
STEROID HORMONES IN THE ADRENAL CORTEX
ADRENOGENITAL SYNDROME (I.E., CONGENITAL ADRENAL HYPERPLASIA)

NOYAUX DES STÉROÏDES

CHOLESTEROL
Biosynthesis
Turnover of Cholesterol
Function of Cholesterol in Membranes
Regulation of Cholesterol Synthesis
Cholesterol Homeostasis

HOPANOIDS, STEROIDS OF PLANTS & INSECTS
Hopanoids
Phyto- and Mycosterols
Ecdysone

ISOPRENOIDS
Terpenes
All-trans Metabolites
Poly-cis Metabolites
Isoprenoid Side Chains

STEROID HORMONES
Biosynthesis
Reaction types
Biological Activation and Regulation of Steroid Hormones
Transport of Steroid Hormones
Degradation of Steroids

GESTAGEN
Biosynthesis of Progesterone
Gestagen Function, Transport and Degradation

ANDROGENS
Biosynthesis
Transport and Degradation
Biological Function of Androgens
Medical Aspects

ESTROGENS
Biosynthesis
Transport and Degradation
Biological Function of Estrogens
Medical Aspects

CORTICOSTEROIDS
Biosynthesis
Transport and Degradation
Biological Function
Glucocorticoids
Mineralocorticoids
Medical Aspects

BILE ACIDS
Occurence
Biosynthesis
Regulation of Biosynthesis
Medical Aspects

TOC
AMINO ACIDS & DERIVATIVES - PROTEIN METABOLISM - NITROGEN METABOLISM
(Hecketsweiler, Protéines Résumé Métabolisme) V1 JPG

PROTEIN SYNTHESIS
CATABOLISM (PROTEIN → PEPTIDE → AMINO ACID)

AMINO ACID
AMINO ACID SYNTHESIS
AMINO ACID DEGRADATION (AMINO ACID → PYRUVATE, ACETYL COA, OR TCA INTERMEDIATE)
UREA CYCLE

BIOSYNTHESIS OF NONESSENTIAL AMINO ACIDS
OVERVIEW
SOURCES OF THE NONESSENTIAL AMINO ACIDS

FUNCTIONS OF AMINO ACIDS
SYNTHESIS OF NEW PROTEINS
SUBSTRATES FOR THE BIOSYNTHESIS
Nonessential amino acids
Purines and pyrimidines
Porphyrins
Neurotransmitters and hormones
CARBON SKELETONS - fuel
Oxidized - energy
gluconeogenesis
fatty acid synthesis

REMOVAL AND DISPOSAL OF AMINO ACID NITROGEN
OVERVIEW
TRANSAMINATION AND OXIDATIVE DEAMINATION
UREA CYCLE
AMMONIA METABOLISM
REMOVAL OF AMINO ACID NITROGEN
DEAMINATION
TRANSDEAMINATION
yields an alpha-keto acid and an ammonium ion (NH4+)
aminotransferase - glutamate dehydrogenase

UREA CYCLE & DETOXIFICATION OF NH4+
NH4+ IS CONVERTED TO UREA
urea cycle
IN PERIPHERAL TISSUES
glutamine synthetase - glutamate - glutamine - glutaminase - NH4+ and glutamate
skeletal muscle - glutamate dehydrogenase - aminotransferase -  alanine
transdeamination - pyruvate and NH4 +
glucose via gluconeogenesis
glycolysis and generates pyruvate
glucose–alanine cycle
HYPERAMMONEMIA
ammonia intoxication
Enzyme defects
carbamoyl phosphate synthetase or ornithine–carbamoyl transferase
metabolite
Treatment

CATABOLIC PATHWAYS OF AMINO ACIDS
OVERVIEW
CARBON SKELETONS OF AMINO ACIDS
METABOLISM OF PHENYLALANINE AND TYROSINE
METABOLISM OF LEUCINE, ISOLEUCINE, AND VALINE: BRANCHED-CHAIN AMINO ACIDS
METABOLISM OF METHIONINE

CARBON SKELETONS OF AMINO ACIDS
GLUCOGENIC, KETOGENIC, OR BOTH
ACETYL COA or ketogenic
Leucine and lysine are only ketogenic
both ketogenic and glucogenic
first step in phenylalanine metabolism
Tyrosine
Epinephrine and norepinephrine—catecholamine hormones secreted by the adrenal medulla
Triiodothyronine and thyroxine
Dopamine and norepinephrine
Melanin
ALPHA-KETOGLUTARATE
Histidine
one-carbon pool
histamine - inflammation
Glutamate
excitatory neurotransmitter - inhibitory neurotransmitter gamma-aminobutyric acid (GABA)
SUCCINYL COA
methionine
S-adenosylmethionine (SAM)
FUMARATE
OXALOACETATE
PYRUVATE FAMILY
sulfhydryl groups of cysteine residues produce sulfate ions
Glycine and serine can furnish one-carbon
Tryptophan - serotonin

NITROGEN FIXATION & METABOLISM
Nitrogen fixation
Nitrogenase
Circulation of nitrogen
Essential amino acids
histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine
Non-essential
alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine

GLUTAMATE, GLUTAMINE, ALANINE, ASPARTATE, ASPARAGINE & AMMONIA TURNOVER
Glutamine Metabolism
Glutamine synthesis
Glutamine conversions and degradation
Glutamate Metabolism
Alanine Metabolism
Aspartate and Asparagine Metabolism
Transamination Reactions

PROLINE & HYDROXYPROLINE

SERINE & GLYCINE
Serine Metabolism
Glycine Metabolism

LYSINE, THREONINE, METHIONINE, CYSTEINE & SULFUR METABOLISM
Common Steps of Biosynthesis and Their Regulation
Lysine Metabolism
Threonine Metabolism
Methionine Metabolism
Cysteine Metabolism
Sulfur Metabolism
Glutathione Metabolism
Reactive Oxygen Species, Damage, and Protection Mechanisms

LEUCINE, ISOLEUCINE & VALINE
Biosynthetic Reactions
Degradation of Branched-Chain Amino Acids

PHENYLALANINE, TYROSINE, TRYPTOPHAN & DERIVATIVES
Biosynthesis of Aromatic Amino Acids
Biosynthesis of Quinone Cofactors
Derivatives and Degradation of Aromatic Amino Acids
Catecholamines
Thyroid Hormones

HISTIDINE

UREA CYCLE, ARGININE & ASSOCIATED REACTIONS
Urea Cycle (Krebs-Henseleit Cycle)
Phosphagens (Phosphocreatine and Phosphoarginine)
Polyamines
UREA CYCLE
Function
Excretion of NH4+ from amino acid metabolism
Location
Partly in the mitochondria and partly in the cytoplasm
Reactants
CO2 and NH4+
Regulation
Products
Urea and fumarate (enters TCA)
Pathophysiology
Ornithine transcarbamylase deficiency
Cycle

AMINO ACID STRUCTURE
Essential
Acidic Amino Acids
Basic Amino Acids

THE AMINO ACID POOL
Replenishment
Depletion

ESSENTIAL & NONESSENTIAL AMINO ACIDS

METABOLIC REACTIONS
Transamination
Oxidative Deamination

NONESSENTIAL AMINO ACID BIOSYNTHESIS
Tyrosine
Serine, Glycine, Cysteine
Alanine
Aspartate, Asparagine
Glutamate, Glutamine, Proline, Arginine

AMINO ACID TISSUE METABOLISM
Amino Acid Transport
Amino Acid Transport Deficiency
Hartnup Disease
Cystinuria
Absorptive State Metabolism

AMINO ACID DERIVATIVES
OVERVIEW
Decarboxylation
Hydroxylation
Methylation
CATECHOLAMINES
HEME SYNTHESIS AND METABOLISM
SEROTONIN, MELATONIN, AND NIACIN SYNTHESIS FROM TRYPTOPHAN
SYNTHESIS OF GAMMA-AMINOBUTYRATE (GABA) FROM GLUTAMATE
SYNTHESIS OF HISTAMINE FROM HISTIDINE
SYNTHESIS OF CREATINE FROM ARGININE, GLYCINE, AND SAM
ASYMMETRIC DIMETHYLARGININE (ADMA)

Methionine Derivative
S-Adenosyl-l-methionine
Tyrosine Derivatives - Catecholamine synthesis/tyrosine catabolism
Thyroid Hormones
Melanin
Catecholamines
Tryptophan Derivatives
Niacin (Vitamin B3
Serotonin
Melatonin
Histidine Derivatives
Histamine
Glycine Derivatives
Heme
Arginine Derivatives
Creatine
Urea
Nitric Oxide
Glutamate Derivative
γ-Aminobutyric Acid
Review of Amino Acid Derivatives

AMINO ACID BREAKDOWN
Removal of the α-Amino Group
Alanine-Glucose Cycle
Disposal of the Carbon Skeleton

AMINO ACID METABOLIC DISORDERS
Phenylketonuria
Tetrahydrobiopterin (BH4) deficiency
Phenylalanine embryopathy
Alkaptonuria
Albinism
Homocystinuria
Maple Syrup Urine Disease
Cystinuria
xxx
Organic acidemias
Propionic acidemia
Methylmalonic acidemia
xxx
CLINICAL RELEVANCE : INHERITED (INBORN) ERRORS OF AMINO ACID METABOLISM
PHENYLKETONURIA (PKU)
ALBINISM
HOMOCYSTINURIA
MAPLE SYRUP URINE DISEASE
HISTIDINEMIA

TOC
TETRAPYRROLES

PATHWAYS FOR THE BIOSYNTHESIS OF TETRAPYRROLES
Biosynthesis of 5-Aminolevulinic Acid (ALA)
Conversion of 5-Aminolevulinic Acid into Uroporphyrinogen III
Conversion of Uroporphyrinogen III into Protoheme
Porphyrias Caused by Enzyme Defects in Humans

HEME & CYTOCHROME BIOSYNTHESIS
Introduction of Iron
Cytochromes Carrying Different Types of Heme

LINEAR TETRAPYRROLES
Heme Oxidation in Humans and Bile Pigment Formation
Plant and Bacterial Linear Tetrapyrroles

BIOSYNTHESIS OF CHLOROPHYLLS

BIOSYNTHESIS OF COBALAMINS (VITAMIN B12 DERIVATIVES)

SIROHEME BIOSYNTHESIS

TOC
NUCLEOTIDES & NUCLEOSIDES - NUCLEOTIDE METABOLISM - NITROGEN METABOLISM

CHEMISTRY OF NUCLEOTIDES
NUCLEOPROTEINS
NUCLEOSIDES
NUCLEOTIDES
NUCLEOTIDES AND NUCLEOSIDES OF BIOLOGICAL IMPORTANCE 220
CYCLIC NUCLEOTIDES

METABOLISM OF PURINES AND PYRIMIDINES
CATABOLISM OF PYRIMIDINES
METABOLISM OF PURINES
SALVAGE PATHWAYS FOR PURINE AND PYRIMIDINE BASES
CATABOLISM OF PURINES
URIC ACID METABOLISM AND CLINICAL DISORDERS OF PURINE AND PYRIMIDINE METABOLISM

OVERVIEW
PURINE METABOLISM
NUCLEOTIDE SALVAGE
PYRIMIDINE METABOLISM
PURINE NUCLEOTIDE CYCLE

ANTICANCER DRUGS INHIBITING NUCLEOTIDE SYNTHESIS
DEGRADATION OF NUCLEOTIDES AND PURINE SALVAGE

NUCLEOTIDE STRUCTURE
THREE UNITS
Sugar
Base
Purines : adenine (A); guanine (G)
Pyrimidines : cytosine (C); thymine (T); uracil (U)
Phosphate
NUCLEOSIDE - NUCLEOTIDE

NUCLEOTIDE FUNCTION
SUBSTRATES FOR DNA SYNTHESIS
SUBSTRATES FOR RNA SYNTHESIS
CARRIERS OF HIGH-ENERGY GROUPS
Phosphoryl
Sugar moieties
Basic moieties
Acyl
Methyl
COMPONENTS OF COENZYMES
REGULATORY MOLECULES

PURINE NUCLEOTIDE SYNTHESIS
ORIGIN OF THE ATOMS IN THE PURINE RING
DE NOVO PURINE NUCLEOTIDE SYNTHESIS
Synthesis of 5'-phosphoribosyl-1-pyrophosphate (PRPP)
committed step - PRPP to 5'-phosphoribosyl-1-amine
IMP
GMP
AMP
REGULATION OF PURINE NUCLEOTIDE SYNTHESIS
PRPP synthetase - ADP and GDP
Glutamine PRPP amidotransferase
steady supply
reciprocal substrate effect
PURINE NUCLEOTIDES CAN ALSO BE SYNTHESIZED BY SALVAGE OF PREFORMED PURINE BASES

PYRIMIDINE NUCLEOTIDE SYNTHESIS
ORIGIN OF ATOMS IN THE PYRIMIDINE RING
DE NOVO PYRIMIDINE SYNTHESIS
Synthesis of carbamoyl phosphate (CAP)
glutamine
synthesis of dihydroorotic acid
single multifunctional enzyme called CAD
Dihydroorotate forms UMP
orotidylate (OMP)
OMP forms uridylate (UMP)
orotic aciduria
Synthesis of the remaining pyrimidine ribonucleotides involves UMP
REGULATION OF PYRIMIDINE SYNTHESIS
SALVAGE
pyrimidine phosphoribosyl transferase
WITH ATP AS THE SOURCE OF HIGH-ENERGY PHOSPHATE (~P), SEVERAL ENZYMES PROVIDE A SUPPLY OF NUCLEOSIDE DIPHOSPHATES AND TRIPHOSPHATES
Adenylate kinase
Nucleoside monophosphate kinases
Nucleoside diphosphate kinase

DEOXYRIBONUCLEOTIDE SYNTHESIS
RIBONUCLEOSIDE DIPHOSPHATES
ribonucleotide reductase
thioredoxin
Strict regulation of ribonucleotide reductase
ENZYME THYMIDYLATE SYNTHASE CATALYZES THE FORMATION OF DEOXYTHYMIDYLATE(dTMP) FROM dUMP
dihydrofolate reductase

NUCLEOTIDE DEGRADATION
PURINE DEGRADATION
uric acid
nucleosides
adenosine deaminase
Purine nucleoside phosphorylase
hypoxanthine and guanine
Hypoxanthine and xanthine
uric acid by the enzyme xanthine oxidase
PYRIMIDINE DEGRADATION
Urinary beta-aminoisobutyrate
indicator of DNA turnover
chemotherapy or radiation therapy

CLINICAL RELEVANCE
DISORDERS CAUSED BY DEFICIENCIES IN ENZYMES INVOLVED IN NUCLEOTIDE METABOLISM
ANTICANCER DRUGS THAT INTERFERE WITH NUCLEOTIDE METABOLISM
GOUT

PURINE NUCLEOTIDES & NUCLEOSIDES
Biosynthesis of Inosine 5'- Phosphate (IMP)
Interconversions of Purine Ribonucleotides
Adenosine 5' -monophosphate (AMP)
Guanosine 5'- monophosphate (GMP)
Regulation of the purine nucleotide biosynthesis
Salvage reactions
ATP and Conservation of Energy
Ribonucleotide Reduction to Deoxyribonucleotides
Interconversions and Degradation of Purine Deoxyribonucleotides
Catabolism of Bases
Medical Aspects

PYRIMIDINE NUCLEOTIDES & NUCLEOSIDES
Biosynthesis of Uridine 5'-Phosphate (UMP)
Interconversions of Pyrimidine Ribonucleotides
Ribonucleotide Reduction and Interconversions of Pyrimidine Deoxyribonucleotides
Catabolism of Bases
Medical Aspects

NUCLEOTIDES
General Structure
Pentose Sugar
Nitrogenous Base
PURINES VERSUS PYRIMIDINES
BASE PAIRING

NUCLEOTIDE SYNTHESIS

DE NOVO PYRIMIDINE & PURINE SYNTHESIS
Pyrimidine synthesis
Leflunomide
5-fluorouracil (5-FU) capecitabine
Purine synthesis
6-mercaptopurine (6-MP) azathioprine
Mycophenolate and ribavirin
Purine and pyrimidine synthesis
Hydroxyurea
Methotrexate (MTX), trimethoprim (TMP),and pyrimethamine

PURINE NUCLEOTIDE SYNTHESIS
De Novo Synthesis
Purine Salvage Pathway

PURINE SALVAGE DEFICIENCIES
Lesch-Nyhan Syndrome
Gout
Severe Combined (T and B) Immunodeficiency - Adenosine deaminasedeficiency

PYRIMIDINE NUCLEOTIDE SYNTHESIS
Hereditary Orotic Aciduria
Nucleotide Degradation

TOC
INTEGRATION OF METABOLISM

METABOLIC EFFECTS OF INSULIN & GLUCAGON

HORMONAL REGULATION OF METABOLISM
OVERVIEW
INSULIN ACTION
GLUCAGON AND EPINEPHRINE ACTION

TOC
FED VERSUS UNFED STATE

THE WELL-FED STATE
OVERVIEW
LIVER METABOLISM: WELL-FED STATE
ADIPOSE TISSUE METABOLISM: WELL-FED STATE
MUSCLE METABOLISM: WELL-FED STATE
BRAIN METABOLISM: WELL-FED STATE

THE FASTING STATE
OVERVIEW
LIVER METABOLISM: FASTING STATE
ADIPOSE TISSUE METABOLISM: FASTING STATE
MUSCLE METABOLISM: FASTING STATE
BRAIN METABOLISM: FASTING STATE

THE STARVATION STATE
OVERVIEW
LIVER METABOLISM: STARVATION STATE
ADIPOSE TISSUE METABOLISM: STARVATION STATE
MUSCLE METABOLISM: STARVATION STATE
BRAIN METABOLISM: STARVATION STATE

FASTED VS FED STATE

METABOLIC FUEL USE
Fasting and starvation
Fed state (after a meal)
Fasting (between meals)
Starvation days 1–3
Starvation after day 3

OVERVIEW
Breakdown of carbohydrates, lipids, and proteins generates ATP or ATP equivalents
Insulin directs how fuel is utilized
The Brain
Muscle Tissue
Adipose Tissue
Glucose Transporters
The Liver

INSULIN & THE FED STATE

STAGES OF STARVATION
Early Starvation (1–3 days)
Late Starvation (3 days or more)

ENDOCRINE PANCREAS
Insulin
Insulin Secretion
Mechanism of Action of Insulin
Insulin and Hyperkalemia
Glucagon
Somatostatin
Molecular Pathways

KETONES
Anabolism
Catabolism
Ketosis
Fasting ketosis
Alcoholic ketoacidosis
Diabetic ketoacidosis (DKA)
Hyperosmolar hyperglycemic non-ketotic syndrome (HHNS)

DIABETES MELLITUS
OVERVIEW
TYPE 1 DM
TYPE 2 DM

ALCOHOL METABOLISM
OVERVIEW
LOW CONCENTRATIONS OF ETHANOL
HIGHER CONCENTRATIONS OF ETHANOL

TOC
MEDICAL NUTRITION & DIET

ENERGY METABOLISM
CALORIC VALUE OF FOODS
BMR
RESPIRATORY QUOTIENT (RQ)
CALORIC REQUIREMENTS
NUTRITIONAL ASPECTS
PROTEIN FACTOR IN NUTRITION
ROLE OF CARBOHYDRATES IN DIET
ROLE OF LIPIDS IN THE DIET
ROLE OF MINERALS IN DIET
BALANCED DIET
PROTEIN-ENERGY MALNUTRITION(PEM)
OBESITY
DIET IN PREGNANCY AND LACTATION
COMPOSITION AND NUTRITIVE VALUE OF COMMON FOODSTUFFS
TEA, COFFEE AND COCOA

KEY DIETARY TERMINOLOGY
OVERVIEW
DRI
RDA
BASAL METABOLIC RATE (BMR)
RESPIRATORY EXCHANGE RATE (RER)
BMI

ENERGY NEEDS
ENERGY REQUIREMENTS
basal energy expenditure (BEE)
lean body mass
thermic effect of food
activity-related expenditure
ENERGY EXPENDITURE
daily energy needs
CALORIC REQUIREMENTS
CALORIC YIELD FROM FOODS
Carbohydrates: 4 kcal/g
Proteins: 4 kcal/g
Fats: 9 kcal/g
Alcohol: 7 kcal/g

MACRONUTRIENTS
DIETARY FUELS
OVERVIEW

DIETARY CARBOHYDRATES 50% to 60%
Available carbohydrates
Monosaccharides
Disaccharides
Polysaccharides
Unavailable carbohydrates - fiber - assist elimination
Insoluble fiber - bulk and shortening intestinal transit time
Soluble fiber
Function
fuel
Inadequate carbohydrate intake
ketosis - wasting
Excess dietary carbohydrates

DIETARY FATS  30%
Saturated fats should make up less than 10% of caloric intake
The essential fatty acids (EFAs) Vitamin F
linoleic acid - linolenic acid
Functions
eicosanoids
carrier for the fat-soluble vitamins
slows gastric emptying
EFA deficiency
artificial formulas - total parenteral nutrition - scaly dermatitis
Excess dietary fat

DIETARY PROTEIN 10% to 20%
nine essential amino acids
Function
Nitrogen balance
positive nitrogen balance
negative nitrogen balance - essential amino acid is missing
recommended adult protein intake

CLINICAL RELEVANCE : protein–energy malnutrition (PEM) syndromes
Marasmus
Kwashiorkor is starvation with edema

CLINICAL RELEVANCE: obesity
Body fat
body mass index (BMI) [Quetelet index]
Diseases that may be associated with obesity

TOC
COFACTORS & VITAMINS

ACTIVE FORMS
VITAMINS
TPP / ThDP (B1) - FMN, FAD (B2) - NAD+, NADH, NADP+, NADPH (B3) - Coenzyme A (B5) - PLP / P5P (B6) - Biotin (B7) - THFA / H4FA, DHFA / H2FA, MTHF (B9) - AdoCbl, MeCbl (B12) - Ascorbic acid (C) - Phylloquinone (K1), Menaquinone (K2) - Coenzyme F420
NON-VITAMINS
ATP - CTP - SAMe - PAPS - GSH - Coenzyme Bb- Cofactor F430 - Coenzyme M - Coenzyme Q - Heme / Haem (A, B, C, O) - Lipoic Acid - Methanofuran - Molybdopterin -  Mycofactocin - PQQ - THB / BH4 - THMPT / H4MPT
METAL IONS
Ca2+ Cu2+ Fe2+, Fe3+ Mg2+ Mn2+ Mo Ni2+ Zn2+

BASE FORMS
VITAMINS

WATER-SOLUBLE VITAMINS
OVERVIEW
Wash out easily from body except B12 and B9.
B12 stored in liver for ~ 3–4 years.
B9 stored in liver for ~ 3–4 months.
B-complex deficiencies often result in dermatitis, glossitis, & diarrhea.
Can be coenzymes (eg, ascorbic acid) or precursors to coenzymes (eg, FAD, NAD+).
FAT-SOLUBLE VITAMINS - ADEK
OVERVIEW
Absorption dependent on bile emulsification, pancreatic secretions, & intact ileum.
Toxicity more common than for water-soluble vitamins because fat-soluble vitamins accumulate in fat.
Malabsorption syndromes with steatorrhea (eg,cystic fibrosis and celiac disease) or mineral oil intake can cause fat-soluble vitamin deficiencies.

A RETINOIDS - RETINOL
Includes retinal, retinol, retinoic acid
BIOSYNTHESIS & INTERCONVERSIONS
BIOCHEMICAL FUNCTION
11-cis-retinal - rhodopsin
beta-carotene - antioxidant
Retinyl phosphate
Retinol & retinoic acid
SOURCES
Retinol
beta-carotene
beta-carotene - Retinol
beta-carotene -  retinoic acid, retinyl phosphate, and 11-cis-retinal
RDA
DEFICIENCY
EXCESS - TOXICITY
Signs and symptoms
Excess beta-carotene is not toxic
CLINICAL USEFULNESS OF SYNTHETIC RETINOIDS
treatment of acne
treatment of psoriasis

B1 (THIAMINE : TPP)
BIOSYNTHESIS
BIOCHEMICAL FUNCTIONS - nerve transmission - coenzyme key enzymes
dehydrogenases
Transketolase
dehydrogenase
SOURCES
RDA
DEFICIENCY - DISORDER - beriberi
Early
Moderately severe: Wernicke-Korsakoff syndrome
Wernicke encephalopathy - Korsakoff syndrome 
Severe
Dry beriberi
Wet beriberi

B2 (RIBOFLAVIN : FAD, FMN)
BIOSYNTHESIS & INTERCONVERSIONS
BIOCHEMICAL FUNCTION
SOURCES
RDA
DEFICIENCY
Angular cheilitis
Glossitis
Scaly dermatitis

B6 (PYRIDOXINE: PLP) pyridoxine, pyridoxamine, and pyridoxal
BIOSYNTHESIS & INTERCONVERSIONS
BIOCHEMICAL FUNCTION
transamination
SOURCES
RDA
DEFICIENCY
Mild
Severe
Other symptoms
CLINICAL USEFULNESS
homocystinuria
PROLONGED HIGH INTAKE
vitamin B6 toxicity with sensory neuropathy

B12 (COBALAMIN) Coenzyme B12
UPTAKE OF THE COENZYME & REDUCTION OF THE VITAMIN
BIOCHEMICAL FUNCTIONS
succinyl CoA
SOURCES
RDA
SIROHEME AND COENZYME F430
DEFICIENCY
Megaloblastic anemia
Paresthesia
irreversible nervous system damage
CAUSES OF VITAMIN B12 DEFICIENCY
Intake of no animal products. Vegans
Impaired absorption

B9 (FOLATE) & PTERINES - FOLIC ACID (pteroylglutamic acid, folacin)
TETRAHYDROFOLATE/FOLYLPOLYGLUTAMATE
GENERAL REACTIONS OF THE C1 METABOLISM
TETRAHYDROBIOPTERIN
MOLYBDENUM/TUNGSTEN COFACTORS
METHANOPTERIN
FUNCTION
tetrahydrofolate
SOURCES
RDA
DEFICIENCY
Megaloblastic anemia
Neural tube defects
homocysteine -  atherosclerotic heart disease
drugs

B5 (PANTOTHENIC ACID : COA) PANTOTHENATE, COENZYME A & ACYL CARRIER PROTEIN (ACP)
BIOSYNTHESIS & INTERCONVERSIONS
BIOCHEMICAL FUNCTION
coenzyme A (CoA)
fatty acid synthase
SOURCE
ADEQUATE INTAKE
DEFICIENCY VERY RARE

B7 (BIOTIN)
BIOSYNTHESIS & INTERCONVERSIONS
Degradation by microorganisms
BIOCHEMICAL FUNCTION
carboxylation enzymes
SOURCES
Bacterial synthesis
Foods
ADEQUATE INTAKE
DEFICIENCY RARE
Signs and symptoms
Raw egg whites contain avidin

B3 (NIACIN : NAD+) NICOTINATE, NAD+, & NADP+ - (nicotinic acid) & niacinamide (nicotinamide)
BIOSYNTHESIS AND DEGRADATION OF NAD+ & NADP+
Salvage reactions
Degradation
MECHANISM OF THE REDOX REACTIONS, STEREOSPECIFICITY
BIOCHEMICAL FUNCTION OF THE NICOTINAMIDE COENZYMES
Niacin is converted to the oxidation–reduction coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)
SOURCES
RDA
DEFICIENCY Hartnup disease
Mild
glossitis
Severe
pellagra - dermatitis, diarrhea, and dementia
EXCESS - HIGH DOSES
very rapid flushing

C (ASCORBIC ACID) ASCORBATE ascorbic acid
BIOSYNTHESIS & METABOLISM
BIOCHEMICAL FUNCTIONS
Coenzyme for oxidation–reduction reactions
Antioxidant
SOURCES
RDA
DEFICIENCY
Mild deficiency: capillary fragility
Severe deficiency: scurvy
EXCESS

D CHOLE CALCIFEROL
BIOSYNTHESIS & INTERCONVERSIONS
BIOCHEMICAL FUNCTIONS
regulation of calcium ion (Ca++) metabolism
absorption - intestinal mucosa
osteoblast
Ca++ reabsorption by the distal renal tubules
SOURCES
Major source - skin - sunlight
Dietary sources
Foods fortified with vitamin D2
ACTIVATION
liver - 25-hydroxycholecalciferol [25(OH)D3]
kidney - 1,25(OH)2D3
Parathyroid hormone (PTH)
REGULATION
MEDICAL ASPECTS
DEFICIENCY
Rickets
Osteomalacia
ADEQUATE INTAKE
EXCESS - TOXICITY
Hypercalcemia
calcification
Bone demineralization
kidney stones

E α-TOCOPHEROL
FUNCTIONS INCLUDE PROTECTION OF MEMBRANES AND PROTEINS FROM FREE-RADICAL DAMAGE
tocopherol
antioxidants
Vitamin C
SOURCES
RDA
DEFICIENCY - impaired lipid absorption
Signs and symptoms
ataxia - myopathy - hemolytic anemia -  retinal degeneration
EXCESS

K PHYLLOQUINONE & MENAQUINONE
FUNCTION
post-translational carboxylation of glutamyl residues
blood clotting factors VII, IX, and X
SOURCES
Foods. Green vegetables
Intestinal flora
ADEQUATE INTAKE (ADULTS)
DEFICIENCY - impairs blood clotting
Causes
VITAMIN K IN INFANTS

TOC
MINERALS & ELECTROLYTES

SODIUM

POTASSIUM

CHLORIDE

CALCIUM
FUNCTIONS
formation of the bones and teeth
normal nerve and muscle function
blood clotting
SOURCES
RDA
DEFICIENCY
Paresthesia
Bone fractures
Osteomalacia

MAGNESIUM
FUNCTIONS
SOURCES
RDA
DEFICIENCY
Increased neuromuscular excitability
Severe hypomagnesemia: depression of PTH release

PHOSPHORUS
FUNCTIONS
phosphorus in the human body is in the bone minerals
Phosphates serve as blood buffers
Phosphate esters are constituents of RNA and DNA
Phospholipids are the major constituents of cell membranes
SOURCES
RDA
DEFICIENCY very rare

TRACE ELEMENTS

OVERVIEW

IRON
FUNCTIONS - heme molecules
Oxygen transport (hemoglobin and myoglobin)
Electron transport (cytochromes)
Activation of oxygen
SOURCES
Foods high in iron
Foods with lesser amounts of iron
RDA
ABSORPTION
DEFICIENCY
anemia
Fatigue
EXCESS - TOXICITY

ZINC
FUNCTIONS
SOURCES
RDA
EXCESS - TOXICITY
metal fume fever,zinc shakes

COPPER

IODINE
FUNCTIONS
thyroid hormones - organification
SOURCES
seafood and iodized salt
RDA
DEFICIENCY
Goiter
Cretinism
INCREASED LEVELS

CHROMIUM

SELENIUM

FLUORIDE

OTHER COMPOUNDS
Lipoate as a Cofactor

TOC
STORAGE & EXPRESSION OF GENETIC INFORMATION - MOLECULAR BIOLOGY - GENE EXPRESSION

TOC
OVERVIEW OF GENE EXPRESSION

INTRODUCTION TO GENETICS   
Genetic code - Central dogma DNA → RNA → Protein - Special transfers RNA→RNA RNA→DNA Protein→Protein
TRANSCRIPTION
Types   
Bacterial - Archaeal - Eukaryotic
Key elements   
Transcription factor - RNA polymerase - Promoter
Post-transcription   
Precursor mRNA (pre-mRNA / hnRNA) - 5' capping - Splicing - Polyadenylation - Histone acetylation and deacetylation
TRANSLATION
Types   
Bacterial - Archaeal - Eukaryotic
Key elements   
Ribosome - Transfer RNA (tRNA)- Ribosome-nascent chain complex (RNC) - Post-translational modification
REGULATION
Epigenetic (imprinting) - Transcriptional (Gene regulatory network cis-regulatory element) - lac operon - Post-transcriptional (sequestration (P-bodies) - alternative splicing - microRNA) - Translational - Post-translational (reversible irreversible)
 
GENETIC INFORMATION
BOTH DNA AND RNA ARE POLYNUCLEOTIDES
nitrogenous base, a sugar, and phosphoric acid
DNA CONTAINS GENETIC INFORMATION
genetic code - four bases - 20 amino acids
three nucleotide sense codon specifies each amino acid
Other properties
contiguous
degenerate
unambiguous - one amino acid
PROTEIN SYNTHESIS
Transcription
Translation
ADDITIONAL INFORMATION
DNA
Messenger RNA (mRNA)
LOCATION
eukaryotic cells
the human body

DNA ORGANIZATION
OVERVIEW
NUCLEOSOMES
PSEUDOGENES
REPETITIVE DNA AND TRANSPOSONS

DNA & RNA: NUCLEIC ACID STRUCTURE
DNA
deoxyribonucleotides - phosphodiester bonds
Shape - double-stranded helix - antiparallel - complementary
Antiparallel
Complementary
base adenine (A) - thymine (T) - base guanine (G) -  base cytosine (C)
Stabilizing forces
hydrogen bonds - complementary - AT two hydrogen bonds - GC - three hydrogen bonds
Stacking and hydrophobic forces - same
RNA
ribonucleotides - 3'-5' phosphodiester bonds
base uracil (U) instead of T
ribose - 2'-OH
Shape
single-stranded helix -  internal double-stranded regions - hairpin loops
messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA)
DENATURATION - unwind or denature
hyperchromic effect, an increase in ultraviolet (UV) absorption (A260)
decrease in viscosity
melting temperature (Tm)
complementary single-stranded regions reassociate in a process called annealing
hybridize - hybridization probes

DNA SYNTHESIS (REPLICATION)
OVERVIEW
THE CELL CYCLE
THE REPLICATION FORK
TELOMERASE
REVERSE TRANSCRIPTASE
DIVIDING CELLS
Mitosis
cell division
interphase - G1, S, & G2 (G = gap, S = synthesis)
G1 phase - euchromatin
DNA synthesis (replication) -  S phase
G2 phase - heterochromatin
REPLICATION
Replication is semiconservative
Catalysis - DNA polymerases (DNAPs)
prokaryotes (e.g., bacteria), polymerase III
eukaryotes - Polymerase delta - mitochondrial DNA
REPLICATION
DNA-unwinding proteins - helicases - Topoisomerases
Primase
makes RNA primers - 5'-to-3' direction
DNAP
leading strand grows continuously in the 5'-to-3 direction
only to the 3'-OH -  discontinuous - “lagging strand”
Okazaki fragments
5'-to-3 exonuclease and polymerase
DNA ligase
ERRORS
3'-to-5' exonuclease - editing
DNA DAMAGE RESULTS FROM A WIDE VARIETY OF AGENTS
Hydrolysis
deamination - depurination - abasic
Oxidation
8-oxo-G
Methylation
UV light creates pyrimidine dimers
Ionizing radiation
strand breaks - ROS
Exogenous chemicals can attack DNA
Carcinogens such as benzo[a]pyrene and dimethylbenzanthracine
Double-strand breaks (DSBs)

DNA REPAIR
BASE EXCISION REPAIR
NUCLEOTIDE EXCISION REPAIR
RECOMBINATIONAL REPAIR
MISMATCH REPAIR
DIRECT REPAIR
DOUBLE-STRAND REPAIR
ANTINEOPLASTIC DRUG ACTION
CLINICAL RELEVANCE
xeroderma pigmentosum
Ataxia telangiectasia, Fanconi’s anemia, Bloom’s syndrome - Cockayne’s syndrome
Hereditary nonpolyposis colon cancer (HNPCC)

DNA DAMAGE AND CANCER
OVERVIEW
PROTOONCOGENES
TUMOR-SUPPRESSOR GENES
DEFECTS IN DNA-REPAIR ENZYMES

TRANSCRIPTION
synthesis of RNA - complementary - DNA template
CATALYSIS. RNA POLYMERASES (RNAPS)
rifampicin
four classes
RNAP I synthesizes rRNA
RNAP II synthesizes mRNA
RNAP III synthesizes tRNA and 5S rRNA
Mitochondrial RNAP
TRANSCRIPTION CYCLE
Binding
promoter sequences -  sense strand - transcription bubble - consensus sequences
Initiation
antisense
Elongation
Actinomycin D
Termination
PROCESSING
processed
primary transcript
heterogeneous nuclear RNA
“cap”
poly(A) tail
intervening sequences, or introns - RNA splicing
Introns begin with GU and end with AG - Small nuclear RNAs
Lariat” structure

TRANSLATION (PROTEIN SYNTHESIS)
AMINO ACID ACTIVATION (INITIAL STEP)
aminoacyl-tRNA synthetase - tRNAs - aminoacyl-tRNAs (AA-tRNAs)
tRNA is the adaptor molecule
AA-tRNA synthetase
anticodon that is antiparallel and complementary to the three-nucleotide codon
high-energy bond
RIBOSOMES
Composition
40S initiation complex
80S initiation complex
PROTEIN SYNTHESIS
Translation initiation
translation start - reading frame
Elongation
incoming AA-tRNA binds to the aminoacyl (A) site
Peptidyl transferase -  with the formation of a peptide bond
peptidyl-tRNA - ribosome moves - peptide chain grows from the N-terminus to the C-terminus
polyribosome or polysome
Termination
nonsense (termination) codon
Wobble
The codon in mRNA (3' base) and the anticodon in tRNA (5' base) (wobble base)

MUTATIONS
TWO PRINCIPAL KINDS
Substitution
Transitions - purine with a purine or a pyrimidine with a pyrimidine
Transversions replace a purine with a pyrimidine
Insertion or deletion
MISSENSE MUTATIONS
different amino acid; nonsense mutations
STRUCTURE OF THE GENETIC CODE TENDS TO MINIMIZE THE EFFECTS OF MUTATION
silent
CLINICAL RELEVANCE: OSTEOGENESIS IMPERFECTA (OI)
CLINICAL RELEVANCE: SICKLE CELL DISEASE
CLINICAL RELEVANCE: RNA TUMOR VIRUSES

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NUCLEIC ACID METABOLISM IN BACTERIA

BACTERIAL DNA REPLICATION
Cell Cycle and Replication
Initiation of Replication
Elongation and Termination
Fidelity of Replication

BACTERIAL DNA REPAIR
DNA Damage
DNA repair systems
Direct Reversal of Damage
Reversal of alkylation
Photoreactivation
Excision Repair Systems
Base excision repair
Nucleotide excision repair (NER)
Mismatch repair
Very short patch repair
Long patch repair
Double-Strand Repair and Recombination
SOS Response (Damage Tolerance Mechanism)

DEGRADATION OF NUCLEIC ACIDS
Exodeoxyribonucleases (Exo-DNases)
Endodeoxyribonucleases (Endo-DNases)
Ribonucleases (RNases)

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NUCLEIC ACID METABOLISM IN EUKARYA

CHEMISTRY OF NUCLEIC ACIDS, DNA REPLICATION AND DNA REPAIR

NUCLEIC ACIDS
JUNK DNA
RIBONUCLEIC ACID (RNA)
SMALL RNAS
TYPES
REPLICATION OF DNA
REPLICATION AND ITS IMPORTANCE
DNA REPAIR MECHANISMS

DNA
DNA Synthesis
DNA Structure

ORGANIZATION OF EUKARYOTIC DNA SUPERCOILING
Heterochromatin
Euchromatin
Chromatin structure
DNA methylation
Histone methylation
Histone acetylation
Histone deacetylation

EUKARYOTIC DNA REPLICATION
Cell Cycle and DNA Replication
Initiation of Replication
DNA Polymerases (Pol)
Replication Forks
Telomeres
Fidelity of Replication

Semiconservative Replication
Separation of Two Complementary DNA Strands
RNA Primer
Chain Elongation
DNA Polymerase I
DNA Ligase

Origin of replication
Replication fork
Helicase
Single-stranded binding proteins
DNA topoisomerases
Primase
DNA polymerase III
DNA polymerase I
DNA ligase
Telomerase

EUKARYOTIC DNA REPAIR
DNA Damage and Principles of Repair
Direct Reversal of Damage
Reversal of alkylation
Photoreactivation
Excision Repair Systems
Base excision repair (BER)
Nucleotide excision repair (NER)
Mismatch Repair
Double-strand Repair and Recombination
Other enzyme activities
Translesion Synthesis (TLS)
DNA Repair and Human Diseases

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MUTATIONS & DNA REPAIR

DEFINITIONS
Mutation
DNA Repair

TYPES OF MUTATIONS IN DNA
Transition
Transversion
Point Mutations - Single nucleotide substitutions
Missense mutations
Nonsense mutations
Silent mutations
Other mutations
Frameshift Mutations
Splice site mutation

Insertions
Frameshift Mutations
Splice Site Mutations
Deletions
Amplifications
Chromosomal Translocations
Reciprocal (non-Robertsonian)
Robertsonian
Interstitial Deletions
Chromosomal Inversions

ORIGINS OF MUTATIONS

MUTAGENS
Chemical Agents
Alkylating Agents
Base Analogs
DNA Intercalating Agents
DNA Cross-Linking Agents
Reactive Oxygen Species
Ionizing Radiation
Ultraviolet Radiation

DNA REPAIR
Single-Strand Damage
Base Excision Repair
Nucleotide Excision Repair (NER)
Mismatch Repair
Double-Strand Breaks
Nonhomologous End Joining
Homologous Recombination

PATHOLOGY
Xeroderma Pigmentosum
Fanconi Anemia
Cockayne Syndrome
Trichothiodystrophy
Ataxia-Telangiectasia
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
Hereditary Breast Cancer
Bloom Syndrome
Werner Syndrome

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SPECIAL BACTERIAL METABOLISM & BIOSYNTHESIS OF ANTIMICROBIALS

BACTERIAL ENVELOPE
Murein synthesis
Gram-negative bacteria
Gram-positive bacteria
Serotyping, diagnosis
Mycobacteria

BACTERIAL PROTEIN EXPORT ACROSS THE CYTOPLASMIC MEMBRANE
Sec-dependent transport
Tat-dependent transport

PROTEIN TRANSPORT ACROSS THE OUTER MEMBRANE OF GRAM-NEGATIVE BACTERIA
Sec/Tat-dependent secretion
Sec-independent secretion

BACTERIAL TRANSPORT SYSTEMS
Passive Transport
Active Transport
Secondary transport systems
Phosphotransferase system (PTS)
ATP-binding-cassette (ABC) transport systems
Iron transport
Efflux Systems

BACTERIAL FERMENTATIONS
Fermentation of Sugars
Fermentations of Non-Sugar Carbon Sources and Especially of Nitrogenous Compounds

ANAEROBIC RESPIRATION
Redox Reactions and Electron Transport
Energy yield
Regulation
Denitrification, Ammonification
Methanogenesis
Energy yield and conservation
Acetogenesis
Reduction of Ferric Ions and Manganese (IV) Ions

CHEMOLITHOTROPHY
Redox Reactions and Electron Transport
Energy Conservation and Reductive Power
Nitrification
Anammox
Sulfur, Hydrogen Sulfide and Thiosulfate Oxidation
Iron Oxidation

QUINOENZYMES, ALKANE AND METHANE OXIDATION
Alkane Oxidation
Quinoenzymes
Oxidation of C1 Compounds
Assimilation of Carbon in Methylotrophs

ANTIBIOTICS
Penicillin and Cephalosporin
Streptomycin
Erythromycin
Tetracycline

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PHOTOSYNTHESIS

LIGHT REACTION
Pathways of electron flow
Structure of the photosystems in higher plants and cyanobacteria
Structure of the photosystem in purple bacteria
Light absorption step
Regeneration of the reaction center
Cytochrome b6f and bc1complexes
NAD+ or NADP+ reduction
Halophilic archaea

DARK REACTIONS
Calvin cycle
Regulation of the Calvin cycle
Photorespiration and C4 cycle

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PLANT SECONDARY METABOLISM

PHENOLICS
Biosynthesis
Shikimate pathway
Polyketide pathway
Phenylpropane Derivatives
Flavonoids
Stilbenes
Tannins

TERPENOIDS
Biosynthesis
Hemiterpenes and Monoterpenes
Sesquiterpenes
Diterpenes
Triterpenes
Cardiac glycosides
Ecdysone
Steroidal alkaloids
Non-glycosylated pentacyclic triterpenes
Saponins (glycosylated pentacyclic triterpenes)
Tetraterpenes
Oligo- and Polyterpenes

NITROGEN-CONTAINING SECONDARY METABOLITES
Cyanogenic Glycosides and Glucosinolates
Cyanogenic glycosides
Glucosinolates
Non-proteinogenic amino acids
Alkaloids
Nicotiana/tobacco alkaloids
Quinolizidine alkaloids
Purine alkaloids
Pyrrolizidine alkaloids
Monoterpene indole alkaloids
Ergoline alkaloids
Benzylisoquinoline alkaloids
Morphine biosynthesis
Tropane alkaloids

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PROTEIN BIOSYNTHESIS, MODIFICATIONS & DEGRADATION

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PROTEIN SYNTHESIS IN BACTERIA

BACTERIAL TRANSCRIPTION
Bacterial RNA Polymerase, Promoters and Initiation of Transcription
Initiation
Elongation
RNA Processing
RNA coding for proteins (mRNA)
Untranslated RNAs
Accuracy of Transcription
Inhibitors of Transcription
Transcription in Prokaryotes
Initiation
Elongation
Termination
Lac operon

REGULATION OF BACTERIAL GENE EXPRESSION
Regulation of Transcription Initiation
Examples for Gene Regulation in Bacteria
Control of the E. coli lacZYA operon
Repression and attenuation of trp loci
Stringent response

BACTERIAL PROTEIN SYNTHESIS
Transfer RNAs and Aminoacyl-tRNA Synthetases
Bacterial Ribosomes and Translational Factors
Bacterial Translation (Polypeptide Synthesis)
Selenocysteine

DEGRADATION OF NUCLEIC ACIDS
Exodeoxyribonucleases (Exo-DNases)
Endodeoxyribonucleases (Endo-DNases)
Restriction endonucleases
Ribonucleases (RNases)

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PROTEIN BIOSYNTHESIS IN EUKARYA

PROTEIN SYNTHESIS, GENE EXPRESSION AND RECOMBINANT DNA
TRANSCRIPTION
GENETIC CODE
TRANSLATION OF M-RNA (PROTEIN SYNTHESIS)
CHAPERONES: PROTEINS THAT PREVENT FAULTY FOLDING
GENE EXPRESSION AND REGULATION
MUTATION
RECOMBINANT DNA TECHNOLOGY

RNA
RNA Versus DNA
Types of RNA
tRNA Structure
Functional organization of a eukaryotic gene
Regulation of Gene Expression at the Level of Transcription - Regulation of gene expression
Promoters
Enhancer
Silencer
Epigenetics
Transcription
RNA Processing (eukaryotes)
Summary of Key Principles of DNA Replication and RNA Transcription
RNA polymerases
Eukaryotes
Prokaryotes
Splicing of pre-mRNA
Introns vs exons

EUKARYOTIC TRANSCRIPTION
RNA Polymerases (Pol)
mRNA Transcription by RNA Pol II
Transcription factors
Initiation
Elongation
Termination
Processing of mRNA
Capping
Splicing
Polyadenylation
snRNA Transcription
rRNA Transcription by RNA Pol I
Processing of rRNA
tRNA Transcription by RNA Pol III
Modification / Processing of tRNAs
5S rRNA Transcription by RNA Pol III
Inhibitors of Transcription

REGULATION OF EUKARYOTIC TRANSCRIPTION
Structure of Core Promoter DNA Elements
RNA polymerase II core promoters
RNA polymerase I core promoters
RNA polymerase III core promoters
Structure of Specific Transcription Factors
Modulation of the Transcription Rate

EUKARYOTIC TRANSLATION
Components of the Translation System
Transfer RNAs
Messenger RNAs
Ribosomes
Translation factors
Polypeptide Synthesis
Initiation
Elongation
Termination
Ribosome recycling

Ribosomes
tRNA Structure
tRNA Charging
tRNA Wobble
Start and stop codons
mRNA start codon Eukaryotes Prokaryotes
mRNA stop codons
Protein Synthesis
Initiation
Elongation
Termination
Post-translational Modifications
Trimming
Covalent alterations
Chaperone protein

FEATURES OF THE GENETIC CODE
Central Dogma
Unambiguous
Degenerate/Redundant - Wobble
Commaless, nonoverlapping
Universal
Direction of DNA, RNA, and Protein Synthesis

TRANSLATIONAL REGULATION

mRNA DEGRADATION

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CELL CYCLE IN EUKARYA

G1 phase (gap)
S phase (synthetic)
G2 phase (gap)
M phase (mitotic)
state called G0

CORE COMPONENTS OF THE CELL CYCLE MACHINERY
Cyclin-dependent kinases (CDKs)
Cyclin-dependent kinase regulators
Cyclin-dependent kinase substrates

CELL CYCLE REGULATION IN YEAST
Regulation of G1 to S-phase transition
Control of the pre-replication complex assembly in yeast

G1 TO S TRANSITION IN MAMMALIAN CELLS
Control of G1 to S transition via exogenous stimuli
Pathological aspects

G2 TO M TRANSITION IN MAMMALIAN CELLS
Nuclear envelope breakdown (NEBD)

MITOSIS IN MAMMALIAN CELLS
Spindle and chromosomal segregation

CELL CYCLE CHECKPOINTS
G1 phase checkpoint
S phase checkpoints
G2 checkpoint responses
Spindle assembly checkpoint
Apoptosis
Pathological aspects
Protein degradation
M (Mitosis or Anaphase) Checkpoint

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POSTTRANSLATIONAL MODIFICATION OF PROTEINS

PROTEIN PROCESSING IN THE ENDOPLASMIC RETICULUM
Protein Synthesis and Import into the Endoplasmic Reticulum
Location of ER proteins
Synthesis of Dolichol-bound Oligosaccharides and N-Glycosylation
Formation of Lipid-anchored Proteins in the ER
Acylation of Proteins

GLYCOSYLATION REACTIONS IN THE GOLGI APPARATUS
Synthesis of Glycoproteins
N-Glycans
O-Glycans
Synthesis of Proteoglycans
Pathways of Protein Glycosylation
Synthesis of Glycolipids

TERMINAL CARBOHYDRATE STRUCTURES OF GLYCOCONJUGATES
Blood Groups

PROTEIN FOLDING, TRANSPORT / TARGETING & DEGRADATION

FOLDING OF PROTEINS
Protein Folding in Bacteria
Disulfide bond formation
Protein Folding in the Eukaryotic Cytosol
Protein Folding in the Eukaryotic Endoplasmic Reticulum (ER)

VESICULAR TRANSPORT AND SECRETION OF PROTEINS
Pathways of Transport
Transport Vesicles

PROTEIN TRANSPORT INTO THE NUCLEUS
Targeting mechanism
Ran-dependent transport mechanism
Ran-independent transport mechanism
Regulation of the nucleoplasmic transport

PROTEIN TRANSPORT INTO MITOCHONDRIA
Targeting mechanism
Transport mechanism

PROTEIN TRANSPORT INTO CHLOROPLASTS
Targeting mechanism
Transport mechanism
Targeting to the outer and inner membrane systems

PROTEIN DEGRADATION
Classification of Peptidases
Reaction Mechanism of Serine Peptidases
Reaction Mechanism of Cysteine Peptidases
Reaction Mechanism of Aspartate Peptidases
Reaction Mechanism of Metallopeptidases
Peptidase Inhibitors

PROTEIN DEGRADATION BY THE UBIQUITIN-PROTEASOME SYSTEM (UPS)
Ubiquitylation
Proteasome
Delivery and degradation

POLYMERASE CHAIN REACTION (PCR) AND REAL-TIME PCR
VARIOUS TYPES OF PCR
ADVANTAGES OF REAL-TIME PCR
REAL-TIME REPORTERS
SYBR® GREEN
REAL-TIME REPORTERS FOR MULTIPLEX PCR
INVESTING IN THE REAL-TIME TECHNIQUE
VIRAL QUANTITATION
LIMITATIONS OF REAL-TIME PCR

HUMAN GENOME PROJECT
ANNOUNCEMENT OF DRAFT SEQUENCE OF HUMAN GENOME
APPROACHES OF GENOME SEQUENCING BY TWO GROUPS
GENOME MAPPING
BENEFITS OF THE PROJECT
PROJECT GOALS AND COMPLETION DATES
ADDITIONAL BENEFITS
THE NEXT STEP: FUNCTIONAL GENOMICS

GENE THERAPY
DISEASES OF GENETIC ORIGIN
ALTERED GENES
WHAT IS GENE THERAPY?
HOW DOES GENE THERAPY WORK?
METHODS OF INSERTING GENETIC MATERIAL INTO HUMAN CHROMOSOMES
GENE TRANSFER VEHICLE
VIRAL VECTORS FOR GENE THERAPY
NON-VIRAL VECTORS: LIPOSOMES 3
GENE THERAPY FOR HAEMATOPOIETIC DERIVED DISEASES
GENE SILENCING
RNA INTERFERENCE
ANTISENSE
SIRNA AS ANTIVIRAL AGENT
GERMLINE GENE THERAPY
WHAT IS THE CURRENT STATUS OF GENE THERAPY RESEARCH?
WHAT FACTORS HAVE KEPT GENE THERAPY FROM BECOMING AN EFFECTIVE TREATMENT FOR GENETIC DISEASE?
WHAT ARE SOME OF THE ETHICAL CONSIDERATIONS FOR USING GENE THERAPY?
FUTURE GENE THERAPY
NEW APPROACHES TO GENE THERAPY
HOW TO DEAL WITH A DOMINANT NEGATIVE?
USE OF RIBOZYMES TECHNOLOGY

BIOCHEMISTRY OF CHOLERA—VIBRIO TOXINS, PATHOGENESIS
CHOLERA
HISTORY AND SPREAD OF EPIDEMIC CHOLERA
ANTIGENIC VARIATION AND LPS STRUCTURE IN VIBRIO
CHOLERAE
ANTIGENIC DETERMINANTS OF VIBRIO CHOLERAE
CHOLERA TOXIN 312 • STRUCTURE OF CHOLERA TOXIN
ENZYMATIC REACTION 313 • CHEMISTRY OF COLONISATION OF THE SMALL INTESTINE
GENETIC ORGANISATION AND REGULATION OF VIRULENCE FACTORS IN VIBRIO CHOLERAE
PATHOGENESIS

TOC
VIRUSES

GENERAL CHARACTERISTICS OF VIRUSES

GENOMIC CHARACTERISTICS OF VIRUSES

STRUCTURE

DNA VIRUSES

PAPILLOMAVIRUS
Life cycle – cell entry and establishment of papillomavirus infection
Replication phase
Virion formati on, assembly and release
Medical aspects

RNA VIRUSES

HEPATITIS C VIRUS
HCV genome
HCV life cycle

RETROVIRUSES

HUMAN IMMUNODEFICIENCY VIRUS (HIV)
Genome structure of HIV-1 and protein processing
HIV replication cycle
Mechanism of reverse transcription
Host cellular antiviral defense system
BIOCHEMISTRY OF AIDS
DISCOVERY OF HIV
RETROVIRAL BACKGROUND
STRUCTURE AND MOLECULAR FEATURES OF HIV
VIRUS LIFE CYCLE
MODES OF TRANSMISSION
NATURAL HISTORY OF HIV INFECTION 
IMMUNOLOGICAL RESPONSE IN HIV
DIAGNOSIS OF HIV INFECTION
ANTIRETROVIRAL THERAPY (ART)

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TRANSPORT - MEMBRANE BIOCHEMISTRY

BASIC PROPERTIES OF MEMBRANES
OVERVIEW
MEMBRANE COMPONENTS
MEMBRANE PROTEINS
FLUID PROPERTIES OF MEMBRANES

TOC
TRANSPORT THROUGH MEMBRANES

MOVEMENT OF MOLECULES & IONS ACROSS MEMBRANES
OVERVIEW
SIMPLE DIFFUSION
FACILITATED DIFFUSION
PRIMARY ACTIVE TRANSPORT
SECONDARY ACTIVE TRANSPORT
HEREDITARY DEFECTS

SYSTEMS OF EUKARYOTIC MEMBRANE PASSAGE
Energy Requirements
TC SYSTEM
1. Channels/Pores
1.A. alpha-Type channels
1.B. beta-Barrel porins
1.C. Pore-forming toxins (proteins and peptides)
1.D. Non-ribosomally synthesized channels
1.E. Holins
1.F. Vesicle fusion pores
1.G. Viral Fusion Pores
1.H. Paracellular channels
2. Electrochemical Potential-driven Transporters
2.A. Porters (uniporters, symporters, antiporters)
2.B. Nonribosomally synthesized porters
2.C. Ion-gradient-driven energizers
3. Primary Active Transporters
3.A. P-P-bond-hydrolysis-driven transporters
3.B. Decarboxylation-driven transporters
3.C. Methyltransfer-driven transporters
3.D. Oxidoreduction-driven transporters
3.E. Light absorption-driven transporters
4. Group Translocators
4.A. Phosphotransfer-driven group translocators
4.B. Nicotinamide ribonucleoside uptake transporters
4.C. Acyl CoA ligase-coupled transporters
5. Transport Electron Carriers
5.A. Transmembrane 2-electron transfer carriers
5.B. Transmembrane 1-electron transfer carriers
8. Accessory Factors Involved in Transport
8.A. Auxiliary transport proteins
8.B. Ribosomally synthesized protein/peptide toxins that target channels and carriers
8.C. Non-ribosomally synthesized toxins that target channels and carriers
9. Incompletely Characterized Transport Systems
9.A. Recognized transporters of unknown biochemical mechanism
9.B. Putative transport proteins
9.C. Functionally characterized transporters lacking identified sequences

1. CHANNELS / PORES
VOLTAGE GATED ION CHANNELS
K+
Voltage Dependent (Kv) KA KSR
Two pore domain (K2p, TASK)
Calcium activated (KCa) BCa
Inward rectifier (KirIRK)
Na+ & Ca++
Nav
Cav T P N
Cl-
& Ca++ act
LIGAND-GATED ION CHANNELS
Cys-loop family of neurotransmitter receptors
5-HT3 (serotonin)
Nicotinic ACh
GABAA
Glycine
Zinc-activated
ATP-gated P2X receptor family
Inotropic glutamate channel family
AMPA
Kainate
NMDA
Orphan (GluD)
Ryanodine and inositol 1,4,5-triphosphate receptor family
Inositol-P3 receptors
Ryanodine receptors
Store-operated Ca++ Channels

2. SOLUTE CARRIERS
Solute : sodium symporter (SSS) family
Neurotransmitter : sodium symporter (NSS) family
Bile acid: sodium symporter (BASS) family
Cation: chloride cotransporter (CCC) family
Dicarboxylic amino acid:cation (Na+ or H+) symporter (DAACS) family
Calcium/cation antiporter family
Mitochondrial carrier (MC) family
UDP-galactose/UMP antiporter family

3. PRIMARY ACTIVE TRANSPORT SYSTEMS
P-Type ATPases
F-Type ATPases
V-Type ATPases
ATP-Binding Cassette transporters

IMPORT BY ENDOCYTOSIS AND PINOCYTOSIS
Endocytosis
Pinocytosis
Clathrin-coated vesicles

THE CYTOSKELETON AS MEANS FOR INTRACELLULAR TRANSPORT & CELLULAR MOVEMENTS IN EUKARYA
Structure of microtubules
Motion during mitosis
Intracellular movement along microtubules
Extracellular movements
Actin filaments
Intermediary filaments

TOC
TRANSPORT OF LIPIDS IN PLASMA

APOLIPOPROTEINS (Apo) - MAJOR
E
AI
CII
B48
B100

PLASMA LIPOPROTEIN METABOLISM
Chylomicron metabolism
VLDL/LDL metabolism
HDL metabolism
Scavenger pathway

LIPID TRANSPORT PROTEINS

LIPOPROTEIN RECEPTORS
LDL receptor
Scavenger receptor
Chylomicron remnant receptor
HDL receptors

LIPID METABOLIC DISORDERS
ABETALIPOPROTEINEMIA
FAMILIAL DYSLIPIDEMIAS
I—Hyper-chylomicronemia
II—Hyper-cholesterolemia
III—Dysbeta-lipoproteinemia
IV—Hyper-triglyceridemia

KEY ENZYMES IN LIPID TRANSPORT
Cholesteryl ester transfer protein
Hepatic lipase
Hormone-sensitive lipase
Lecithin-cholesterol acyltransferase
Lipoprotein lipase
Pancreatic lipase
PCSK9

LIPOPROTEIN FUNCTIONS
Chylomicron
VLDL
IDL
LDL
HDL

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OXYGEN TRANSPORT BY HEMOGLOBIN

BIOSYNTHESIS & PROPERTIES OF HEMOGLOBIN & MYOGLOBIN
Hemoglobin
Heme biosynthesis
Globin biosynthesis
Structure

OXYGEN BINDING TO HEMO- AND MYOGLOBIN
Hemoglobin oxigenation
Dissociation curves

HEMOGLOBIN DISEASES IN HUMANS

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SIGNAL TRANSDUCTION & CELLULAR COMMUNICATION - RECEPTORS & SIGNAL TRANSDUCTION CASCADES

OVERVIEW
SEQUENCE OF EVENTS IN CELL-CELL SIGNALING
GENERAL PROPERTIES OF CELL-SURFACE RECEPTORS
COMMON FEATURES OF G PROTEIN–COUPLED RECEPTORS (GPCRS)
CYCLIC AMP (CAMP) PATHWAY
PHOSPHOINOSITIDE PATHWAY
RECEPTOR TYROSINE KINASES (RTKS)
INTRACELLULAR RECEPTORS FOR LIPOPHILIC HORMONES
CLINICAL ASPECTS OF CELL-CELL SIGNALING

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INTER-CELLULAR SIGNAL TRANSMISSION BY HORMONES

GENERAL CHARACTERISTICS OF HORMONES

GENERAL CHARACTERISTICS OF RECEPTORS
Kinetics of hormone binding

INSULIN AND GLUCAGON
Insulin
Glucagon

EPINEPHRINE AND NOREPINEPHRINE (CATECHOLAMINES)

HYPOTHALAMUS-ANTERIOR PITUITARY HORMONE SYSTEM
Hypothalamo-pituitary-adrenal axis
Hypothalamo-pituitary-thyroid axis
Hypothalamo-pituitary-liver/bone axis
Hypothalamo-pituitary-testis axis
Hypothalamo-pituitary-ovary/uterus axis

PLACENTAL HORMONES

HORMONES REGULATING THE EXTRACELLULAR CA++, MG++ AND PHOSPHATE CONCENTRATIONS
Calcium
Magnesium

HORMONES REGULATING THE NA+ CONCENTRATION AND THE WATER BALANCE
Na+ turnover
Water turnover

HORMONES OF THE GASTROINTESTINAL TRACT
Gastric hormones
Pancreatic hormones

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NERVE CONDUCTION & SYNAPTIC TRANSMISSION

MEMBRANE POTENTIAL
Equilibrium potential

CONDUCTION OF THE ACTION POTENTIAL ALONG THE AXON

TRANSMITTER GATED SIGNALLING AT THE SYNAPSE
Presynaptic reactions
Postsynaptic reactions
Direct transmitter gating (receptors type I, ionotropic receptors, ligand-gated ion channels) GABA, glycine, glutamate and aspartate
Indirect transmitter gating (receptors type II, metabotropic receptors) Norepinephrine, dopamine, serotonin,acetylcholine,neuropeptides
Integration of signals

VOLTAGE GATED SIGNALLING AT THE SYNAPSE
Electrical synapses. Modulation by phosphorylation

POSTSYNAPTIC RECEPTORS

ACETYLCHOLINE
N (I)
M1 (neuronal), M3 (glandular), M5 (II)
M2 (cardiac), M4 (II)

NOREPINEPHRINE, EPINEPHRINE
Beta1, Beta2, Beta3 (II)
Alpha1 (II)
Alpha2 (II)

DOPAMINE
D1, D5 (II)
D2a (II)
D2b (II)
D3, D4 (II)

SEROTONIN
5-HT1 (II)
5-HT2 (II)
5-HT3 (I)

GABA
GABAA
GABAB

GLYCINE
(I)

GLUTAMATE
NMDA (N-methyl-D-aspartate) (I)
Kainate (I)
AMPA (quisqualate receptor) (I)
mGlu (II)

ENKEPHALINS, DYNORPHINE & Beta-ENDORPHIN
d, m, k opioid (II)

AXONAL TRANSPORT
Fast axonal transport of membrane-associated organelles
Anterograde
Mitochondrial
Retrograde
Slow axonal transport of cytoskeleton- and cytoplasmic components
type A
type B

TOC
PRINCIPLES OF INTRA-CELLULAR COMMUNICATION

Direct transmitter gated ion channels (I)
Members of a large family of seven transmembrane receptors (7TMRs) are coupled to heterotrimeric G-proteins (II)
Signaling via heterotrimeric G-proteins can lead to subsequent:
activation of adenylate cyclase
activation of phospholipase C causing activation of protein kinase C causing release of inositol phosphates
activation of cGMP phosphodiesterase
activation of phospholipase A2
Many receptors for growth factors & cytokines either have tyrosine kinase activity themselves or can associate with and activate cytoplasmic tyrosine kinases
The receptors binding steroid or thyroid hormones or retinoic acid act themselves as transcription factors
Guanylate cyclase can also be a hormone receptor

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RECEPTORS COUPLED TO HETEROTRIMERIC G-PROTEINS

MECHANISM OF HETEROTRIMERIC G-PROTEIN ACTION
Galpha SUBUNITS
Gs Family
Gi Family
Gq Family
G12 Family
Gbetadelta SUBUNITS
Pathogenic reactions

cAMP METABOLISM, ACTIVATION OF ADENYLATE CYCLASE & PROTEIN KINASE A
cAMP
Adenylate cyclase
Protein kinase A (PKA)

ACTIVATION OF PHOSPHOLIPASE C & PROTEIN KINASE C
Phospholipases C (PLC)
Inositol (1,4,5)-P3 (IP3)
1,2-Diacylglycerol (DAG, mostly 1-stearoyl-2-arachidonyl-sn-glycerol)
Other isoforms of phospholipase C
Protein kinases C
Other isoenzymes of PKC

METABOLIC ROLE OF INOSITOL PHOSPHATES & CA++
Ca++ concentration in cells
Release of Ca++ from intracellular stores in animals
Inositol(1,4,5)-P3 receptor Ca++ channels (IP3R, e.g., in Xenopus oocytes)
Ryanodine receptor (RYR) Ca++ channels open
Both types of channels
Role of calmodulin
Metabolism of inositol phosphates
Reconstitution of phosphatidylinositol phosphates

MUSCLE CONTRACTION
Contraction of striated muscles
Regulation of striated muscle contraction
Cardiac (heart) muscle
Structure of smooth muscles
Contraction of smooth muscles
Calcium-dependent contraction
Calcium-independent contraction
Nonmuscle cells

VISUAL PROCESS
Rods
Cones

OLFACTORY & GUSTATORY PROCESSES
Olfactory process
Gustatory process

ARACHIDONATE METABOLISM & EICOSANOIDS
Release of arachidonic acid
The cytoplasmic phospholipase A2
The non-pancreatic, secretory phospholipases A2
Phospholipases C and D
Biosynthesis of prostanoids by the cyclooxygenase pathway
Biosynthesis of leukotrienes (LT) by the lipoxygenase pathway
Epoxygenase P-450 pathway

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RECEPTORS ACTING THROUGH TYROSINE KINASES

REGULATORY FACTORS FOR CELL GROWTH & FUNCTION
Competence factors
for transition from the resting phase G0 to the G1 phase of the cell cycle or for bypassing G0 altogether (e.g.,EGF, TGF-a, FGF, PDGF and IL-2)
Progression factors
for passage through the restriction (commitment) point in the G1 phase of the cell cycle & initiation of DNA replication & cellular division (e.g., IGF-1 or insulin in high concentrations)
Antagonists of cell cycle progression
e.g., transforming growthfactor-b (TGF-b), interferons or tumor necrosis factor a (TNFa)
Compounds, which additionally cause different effects
[ e.g., insulin, regulating glucose levels or cytokines, controlling chemotaxis ]
Oncogenes

COMPONENTS OF THE SIGNAL CASCADES
Membrane associated receptors
which contain an extracellular ligand binding domain, a transmembrane domain, & either an intracellular tyrosine kinase domain or a binding site for a cytosolic tyrosine kinase
Protein tyrosine kinases
Protein serine/threonine kinases
Mixed lineage kinases (MLKs)
phosphorylating tyrosine and serine/threonine residues
Protein phosphatases,
counteracting the kinases
Small G-proteins
(different from heterotrimeric G-proteins)
GDP/GTP exchange and guanosine nucleotide releasing factors
Transcription factors

RECEPTOR TYROSINE KINASES
Receptor structure
EGF receptor activation of the MAPK pathway
Insulin receptor activation of the PI 3K pathway
Other signal transduction pathways
Crosstalk with other signaling systems
Ras related small, monomeric G proteins

Vertebrate Receptor Families With Integral Protein-Tyrosine Kinase Activity (RTK)
Epidermal growth factor (EGF) receptor family
Insulin receptor family
Platelet derived growth factor (PDGF)/macrophage colony stimulating factor (M-CSF) receptor family
Fibroblast growth factor (FGF) receptor family
Vascular endothelial cell growth factor (VEGF) receptor family
Hepatocyte growth factor (HGF) receptor family
Neurotropin receptor family
Eph-like receptor tyrosine kinases (largest family)
Axl receptor tyrosine kinase

“Small” G-proteins, GDP/GTP Exchange Factors & Linker Proteins
Ras (p21, 3 isotypes)
Rap1a
Rac, Rho, Ran, Arf, Rab, other Ras-related small G-proteins (ca. 21 kDa)
GRF (GEF, GNRP)
GAP
Shc
IRS1

‘Downstream’ Protein Kinases, Counteracting Phosphatases & Transcription Factors
MAPKKK (S/T)
MAPKK (T/Y)
MAPK (S/T)
AP

TYROSINE KINASE-ASSOCIATED RECEPTORS (TKaR)
CYTOKINE RECEPTORS
Type I cytokine receptor family (CRF1)
The IL-2 receptor family
The gp140 family
The gp130 family
The growth hormone receptor family
The type II cytokine / interferon receptor family (CRF2)
The type III or TNF-receptor family
The type IV cytokine (Ig superfamily / interleukin-1) receptor and Toll-like receptors
Interleukin-1 receptors/Toll-like receptors (TLRs)
Ras/Raf/MAPK pathway
JAK/STAT pathway
STAT activation
T CELL RECEPTORS (TCRs)
B CELL RECEPTORS (BCRs)

Protein-Tyrosine Kinases Associated With Receptors
Src family
Jak family
Syk family
Other

Some Specific Transcription Factors
Elk-1,SAP-1
Ets
Fos
Jun
Myc
STAT (1 … 4)

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PROGRAMMED CELL DEATH (APOPTOSIS)

Intrinsic apoptosis pathway
Extrinsic apoptosis pathway
Receptor-induced apoptosis
Death receptors
Dependence receptors

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RECEPTORS FOR STEROID & THYROID HORMONES, FOR RETINOIDS & VITAMIN D

Group A receptors
Group B receptors

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CYCLIC GMP DEPENDENT PATHWAYS AND EFFECTS OF NITRIC OXIDE (NO)

Membrane Bound Guanylate Cyclases
GC-A and -B
GC-C
Soluble Guanylate Cyclases & Their Activation by Nitric Oxide (NO)
NO metabolism
Types of Eukaryotic NO Synthase : nNO synthase (neuronal, Type I) eNO synthase (endothelial, Type III) iNO synthase (inducible, Type II)
Protein Kinase G (PKG)

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IMMUNE SYSTEM

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COMPONENTS OF THE IMMUNE SYSTEM

INNATE, NON ADAPTIVE IMMUNE SYSTEM
Soluble Factors
Direct effect
Indirect effect
Cells of the Innate Immune System
Danger Receptors
Toll like receptors (TLR)
Intracellular receptors
Nod-like receptors (NLR)
RIG-like receptors (RLR)

SPECIFIC, ADAPTIVE IMMUNE SYSTEM

DEVELOPMENT AND MATURATION OF THE CELLULAR COMPONENTS

ANTIGEN RECEPTOR OF B LYMPHOCYTES, ANTIBODIES
Immunoglobulins
Structure and recombination of immunoglobulin genes
Generation of diversity
Classes of immunoglobulins
Antigen receptor complex on B lymphocytes
Biological Function of Human Immunoglobulin Isotypes

COMPLEMENT SYSTEM
Classical pathway
Lectin pathway
Alternative pathway
Formation of the ‘membrane-attack complex’ (MAC), lysis of pathogens and cells
Other effects of the complement system
Solubilization of immune complexes
Opsonization of pathogens
Induction of inflammation
Control mechanism of the complement system
Medical aspects

ANTIGEN RECEPTOR OF T LYMPHOCYTES
Structure of the T cell receptor (TCR)

ANTIGEN PRESENTATION BY MHC MOLECULES
MHC Class I molecules
MHC Class II molecules
Processing and presentation of antigens for T lymphocytes
Gamma/DeltaT cells

CYTOKINES, CHEMOKINES & RECEPTORS
Cytokines
Cytokine receptors
Type I or hematopoietin receptors, also called the cytokine receptor superfamily
Type II or interferon receptors
Type III or TNF receptors
Type IV or Ig superfamily receptors
TGF (transforming growth factor) family receptors
The chemokine receptors
Chemokines

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GENERATION OF A SPECIFIC IMMUNE RESPONSE

ACTIVATION OF T CELLS
CD4+ T lymphocytes
CD8+ T lymphocytes

CD4+ T EFFECTOR CELLS, REGULATION OF THE IMMUNE RESPONSE
Th1 cells
Th17 cells
Th2 cells
Regulatory T cells
Natural Treg
Adaptive regulatory T cells

ACTIVATION OF B CELLS

LYMPHOCYTE CIRCULATION AND GENERATION OF CELLULAR & HUMORAL IMMUNE RESPONSES IN LYMPHOID TISSUE
Cessation of an adaptive immune response

CELLULAR CYTOTOXICITY & APOPTOSIS
Extrinsic pathway
Receptor-induced apoptosis
Granzyme-induced apoptosis
Intrinsic (mitochondrial) pathway
Cytotoxic CD8+ T cells
Natural killer cells (NK cells)

INTERACTIONS BETWEEN THE IMMUNE SYSTEM & THE NEUROENDOCRINE SYSTEM
Inflammatory cytokines
Inflammatory mediators

IMMUNOLOGICAL TOLERANCE
Central (recessive) tolerance
Peripheral (dominant) tolerance
Clonal anergy
Immunological ignorance
Suppression by regulatory T cells

INDUCTION OF SPECIFIC IMMUNE RESPONSES AGAINST PATHOGENS

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PATHOLOGIC IMMUNE RESPONSES

IGE-MEDIATED HYPERSENSITIVITY OF THE IMMEDIATE TYPE

AUTOIMMUNITY

Genetic predisposition
Environmental factors
Hormonal influence
Incomplete elimination of autoreactive lymphocytes
Epitope spreading

Modification of self proteins
Activation of autoreactive T cells in inflammatory environment
Molecular mimicry
Superantigen stimulation

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ADHESION OF LEUKOCYTES
Rolling
P-Selectin
E-Selectin
L-Selectin
Adhesion
Flattening of the cells and diapedesis
Other adhesion reactions
Embryonic development
Maintaining correct contacts
Aggregation of platelets
Tumor cell migration

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BLOOD COAGULATION & FIBRINOLYSIS

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HEMOSTASIS
Regulation
coagulation cascade
inner endothelial cell lining & inhibitors in the plasma
feedback inhibition mechanisms
After an injury, the following reactions take place:
vasoconstrictive compounds
Platelets
coagulation cascades
second phase of clot expansion
coagulation inhibitors

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INITIAL REACTIONS
‘extrinsic pathway’
‘contact activation’ or ‘intrinsic pathway’

REACTIONS INITIATED BY THE TISSUE FACTOR

CONTACT ACTIVATION
Bradykinin
Plasma kallikrein  Plasmin

GENERATION OF BINDING SURFACES
negatively charged phospholipids
Proteins  which form complexes

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COAGULATION PROPAGATION & CONTROL

REQUIREMENTS FOR PROTEASE ACTIVITY

PATHWAYS LEADING TO THROMBIN

KEY EVENTS

CONTROLLED PROPAGATION

GENERATION OF FIBRIN

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PLATELETS (THROMBOCYTES)

integral membrane glycoproteins
linker proteins

Vascular effects
Change of platelet shape
Platelet aggregation and clot formation
Microparticle formation
Control of coagulation

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FIBRINOLYSIS

PATHWAYS OF PLASMINOGEN ACTIVATION
tissue plasminogen activator (t-PA)
Urokinase type plasminogen activator (u-PA)
contact activation of coagulation

CONTROL OF FIBRINOLYSIS

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CONNECTIVE

CLASSIFICATION
Composition
Loose connective tissue
Dense irregular connective tissue
Dense regular connective tissue
Function
Structural
Support
Nutrition
Defense

GROUND SUBSTANCE
Proteoglycans
Glycosaminoglycans
Glycoproteins
Basal Lamina (Basement Membrane)
Fibronectin
Laminin

FIBERS
Type I
Type II
Type III
Type IV
Collagen Fibers
Collagen Synthesis and structure
Clinical Considerations
Scurvy
Osteogenesis imperfecta
Ehlers-Danlos syndrome
Menkes disease
Reticular Fibers
Elastic Fibers
Elastin
Fibrillin-I
Marfan syndrome
Homocystinuria

CELLS
Resident Cells
Transient Cells

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Ethanol metabolism


FED VERSUS UNFED STATE

FASTED VS FED STATE

METABOLIC FUEL USE
Fasting and starvation
Fed state (after a meal)
Fasting (between meals)
Starvation days 1–3
Starvation after day 3

OVERVIEW
Breakdown of carbohydrates, lipids, and proteins generates ATP or ATP equivalents
Insulin directs how fuel is utilized
The Brain
Muscle Tissue
Adipose Tissue
Glucose Transporters
The Liver

INSULIN & THE FED STATE

STAGES OF STARVATION
Early Starvation (1–3 days)
Late Starvation (3 days or more)

ENDOCRINE PANCREAS
Insulin
Insulin Secretion
Mechanism of Action of Insulin
Insulin and Hyperkalemia
Glucagon
Somatostatin
Molecular Pathways

FATTY ACID METABOLISM
Fatty Acid Synthesis
Fatty Acid Synthase
Fatty Acid Oxidation

KETONES
Anabolism
Catabolism
Ketosis
Fasting ketosis
Alcoholic ketoacidosis
Diabetic ketoacidosis (DKA)
Hyperosmolar hyperglycemic non-ketotic syndrome (HHNS)

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LIPOPROTEINS
Function and Structure
Chylomicrons and Remnants
VLDL, IDL, and LDL
HDL
Lipases
Dyslipidemias

SPECIAL LIPIDS
Cholesterol
Anabolism
Cholesterol Derivatives
Glycerophospholipids and Sphingolipids
Structure and Function
Glycerophospholipids
Sphingolipids
Lysosomal Storage Diseases
Sphingolipidoses
Mucopolysaccharidoses
Mucolipidoses
Other Lysosomal Storage Diseases
Eicosanoids

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HEME
Structure
Heme Proteins
Heme Synthesis
Defects in Heme Synthesis
Porphryias
Lead Poisoning
Heme Catabolism
Pathway
Causes of Elevated Bilirubin
Hemoglobin
Structure
Hemoglobin Isotypes
Allosteric Effectors
Methemoglobinemia
Carbon Monoxide Poisoning
Carbon Dioxide

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TOC
HORMONES

OVERVIEW
endocrine system - endocrine glands - hormones
hormones - target tissues

CLASSIFICATION OF HORMONES
WATER-SOLUBLE HORMONES
Catecholamine hormones
Peptide hormones
Protein hormones
LIPID-SOLUBLE HORMONES
Steroid hormones
Thyroid hormones

MECHANISMS OF HORMONE ACTION
WATER-SOLUBLE HORMONES
membrane receptors
intracellular second messengers
adenylate cyclase
adenosine 3',5'-monophosphate (cAMP) - protein kinase A
enzymes
cAMP-responsive element-binding proteins (CREB)
phospholipase C
phosphatidylinositol 4,5-bisphosphate (PIP2) - inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)
DAG -  protein kinase A
IP3 - Ca2+
third group of receptors stimulates tyrosine kinase
autophosphorylation
LIPID-SOLUBLE HORMONES
intracellular hormone receptor proteins
hormone response elements in DNA and alter gene expression

HORMONES THAT REGULATE FUEL METABOLISM
INSULIN
beta-cells in the pancreatic islets of Langerhans
Actions
adipose , skeletal muscle, liver - to lower - blood glucose - nonesterified fatty acid
Increased glucose entry into adipose tissue and muscle
Increased glucose metabolism in adipose tissue, muscle, and liver
Increased amino acid entry into muscle
Decreased lipolysis and fatty acid release in adipose tissue
Secretion
High levels of blood glucose - amino acids increase
epinephrine decreases
GLUCAGON
alpha-cells of the pancreatic islets
Actions
increases blood glucose and fatty acid concentration - cAMP - liver and adipose
Increased glycogenolysis in liver and muscle
Increased gluconeogenesis in liver
Increased functioning of the glucose–alanine cycle between liver and muscle
Increased lipolysis and fatty acid release in adipose tissue
Secretion
Low levels of blood glucose - high levels of blood amino acids both increase
EPINEPHRINE
adrenal medulla, is a catecholamine
Actions
elevates blood glucose and fatty acids and provokes the fight-flee reflex
Increased glycogenolysis in muscle and liver
Increased lipolysis and fatty acid release in adipose tissue
Development of the fight-flee reflex
Secretion
hypoglycemia, low oxygen tension - neural factors stimulate epinephrine secretion
CORTISOL
Actions - elevation of blood glucose
Increased muscle protein breakdown, which releases amino acids as substrates for gluconeogenesis
Increased synthesis of gluconeogenic enzymes in the liver
Inhibition of insulin action
Increased total body fat at the expense of muscle protein
Increased water excretion by the kidney
Inhibition of inflammation
Suppression of the immune system
Increased resistance to stress
Secretion
Adrenocorticotrophic hormone (ACTH) - Corticotropin-releasing hormone (CRH)

HORMONES THAT REGULATE SALT & WATER BALANCE
ALDOSTERONE adrenal cortex, is a steroid hormone
Actions
Aldosterone stimulates Na+ retention and K+ secretion by the kidney, sweat glands, and intestinal mucosa
Secretion
renin–angiotensin system and elevated blood K+ both stimulate aldosterone secretion
ARGININE VASOPRESSIN (AVP)
posterior pituitary
Actions
AVP stimulates water reabsorption by the kidney
Secretion
High plasma osmolality and neural impulses both stimulate AVP secretion

HORMONES THAT REGULATE CALCIUM & PHOSPHATE METABOLISM
PARATHYROID HORMONE (PTH)
parathyroid glands
Actions - PTH raises plasma calcium and lowers plasma phosphate
Stimulation of osteoclasts, leading to dissolution of bone salts and release of Ca2+ and PO4 3- into the blood
Decreased Ca2+ excretion and increased PO4 3- excretion by the kidney
Stimulation of calcitriol formation from 25OH-D3 by the kidney, thus leading to increased calcium absorption from the intestine
Secretion
Hypocalcemia stimulates secretion of PTH, and hypercalcemia inhibits it
CALCITRIOL - 1,25-dihydroxycholecalciferol [1,25(OH)2-D3], is derived from vitamin D3
Synthesis
Vitamin D3 is converted to calcitriol by two hydroxylation reactions, one in the liver and one in the kidney
Hypocalcemia and PTH stimulate the second hydroxylation reaction
Calcitriol is released from the kidney into the circulation
Actions
Stimulation of calcium absorption from the gut
Increased efficiency of PTH action on bone

HORMONES THAT REGULATE BODY SIZE & METABOLISM
THYROXINE and TRIIODOTHYRONINE
thyroid follicle
Actions -  increase in metabolic rate
Increased heat production
Increased growth
Increased mental activity
Increased sensitivity to epinephrine
Increased catabolism of cholesterol, leading to decreased blood cholesterol
Secretion
Thyroid-stimulating hormone (TSH) - anterior pituitary regulates
Hypothalamic thyrotropin-releasing hormone stimulates TSH secretion, and high levels of plasma thyroxine suppress it
HUMAN GROWTH HORMONE (HGH)
anterior pituitary
Actions
Stimulation of the liver to secrete insulin-like growth factor I (IGF-1), which is responsible for several of the anabolic effects of growth hormone
Increased protein synthesis in hard and soft tissues
Increased bone calcification and bone matrix formation
Increased amino acid uptake in muscle, bone, and kidney
Increased blood glucose (antagonistic to the action of insulin)
Increased fatty acid release from adipose tissue
Secretion
Growth hormone–releasing hormone and growth hormone release–inhibiting hormone (somatostatin), both from the hypothalamus, regulate HGH secretion

HORMONES THAT REGULATE THE MALE REPRODUCTIVE SYSTEM
TESTOSTERONE - interstitial cells of the testes
Primary functions
Spermatogenesis [if follicle-stimulating hormone (FSH) is also present]
Maturation and function of the prostate and seminal vesicles
Maturation of male sex organs (i.e., penis and scrotum)
Interest and ability to engage in sexual activity
Additional actions
Pubertal growth spurt (i.e., increased muscle mass and longitudinal growth)
Maturation of the skin and male pattern of hair distribution
Deepening of the voice
Aggressive personality
FSH - along with testosterone, stimulates spermatogenesis
SECRETION - LUTEINIZING HORMONE (LH) from the anterior pituitary stimulates testosterone secretion from the testes, and gonadotropin-releasing hormone (GnRH) from the hypothalamus regulates FSH and LH secretion

HORMONES THAT REGULATE THE FEMALE REPRODUCTIVE SYSTEM
ESTRADIOL - which prepares the female reproductive system for pregnancy, is a phenolic steroid secreted by the ovarian follicle
Actions in the female reproductive system
Maturation of the uterus, cervix, and vagina
Proliferation of the vaginal epithelium and uterine endometrium
Duct proliferation and fat deposition in the mammary glands
Effects outside the reproductive system
Increased bone calcification and closure of the epiphyses
Skin maturation and female hair distribution
Female pattern of fat distribution
PROGESTERONE - which promotes gestation in women who have been prepared by the actions of estradiol, is a steroid hormone secreted by the corpus luteum
Transformation of the proliferative endometrium to a secretory endometrium
Prevention of synchronized uterine muscle contraction
Maintenance of pregnancy
Stimulation of growth of the mammary gland system for milk secretion
GNRH PRODUCTION RESULTS IN SECRETION OF FSH AND LH - Cyclic secretion of GnRH by the hypothalamus accounts for the menstrual cycle
FSH stimulates growth of the ovarian follicle and secretion of estradiol by follicular granulosa cells
A burst of LH and FSH secretion stimulates ovulation, with rupture of the follicle and release of the ovum
LH stimulates formation and function of the corpus luteum, which secretes progesterone and estradiol
PROLACTIN from the anterior pituitary stimulates milk production in mammary glands that have been prepared by estradiol and progesterone
OXYTOCIN from the posterior pituitary stimulates milk ejection from the mammary glands

CLINICAL RELEVANCE: DIABETES MELLITUS
INSULIN-DEPENDENT DIABETES MELLITUS (IDDM, TYPE I DIABETES)
nonexistent insulin secretion
NON-INSULIN-DEPENDENT DIABETES MELLITUS (NIDDM, TYPE II DIABETES)
deficiency in insulin secretion relative to blood glucose



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GENETICS xxxxxxxxxxxxxxxxxxxxxxxxxxxx

GENETIC TERMS
Codominance
Variable expressivity
Incomplete penetrance
Pleiotropy
Anticipation
Loss of heterozygosity
Epistasis
Aneuploidy
Dominant negative mutation
Linkage disequilibrium
Mosaicism
McCune-Albright syndrome
Locus heterogeneity
Allelic heterogeneity
Heteroplasmy
Uniparental disomy

HARDY-WEINBERG POPULATION GENETICS

NON–SEX CHROMOSOME DISEASES
AUTOSOMAL DOMINANT
Achondroplasia, autosomal dominant polycystic kidney disease, familial adenomatous polyposis,
familial hypercholesterolemia, hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu
syndrome), hereditary spherocytosis, Huntington disease, Li-Fraumeni syndrome, Marfan syndrome,
multiple endocrine neoplasias, myotonic muscular dystrophy, neurofibromatosis type 1 (von
Recklinghausen disease), neurofibromatosis type 2, tuberous sclerosis, von Hippel-Lindau disease
AUTOSOMAL RECESSIVE
Mostly consist of enzyme defects. Oculocutaneous albinism, phenylketonuria, cystic fibrosis, sickle
cell disease, Wilson disease, sphingolipidoses (except Fabry disease), hemochromatosis, glycogen
storage diseases, thalassemia, mucopolysaccharidoses (except Hunter syndrome), Friedreich
ataxia, Kartagener syndrome, ARPKD. Oh, please! Can students who score high grades tell me
features of the kidney disorder Autosomal Recessive Polycystic Kidney Disease?
Cystic fibrosis
SEX CHROMOSOME DISEASES
X-LINKED RECESSIVE
X-inactivation (lyonization)
X-LINKED DOMINANT
MITOCHONDRIAL DISEASES
Mitochondrial myopathies
Leber hereditary optic neuropathy

MUSCULAR DYSTROPHIES
Duchenne XR
Gowers sign
Becker XR
Myotonic dystrophy AD

Rett syndrome
Fragile X syndrome XD

Trinucleotide repeat expansion diseases
Huntington disease
Myotonic dystrophy
Fragile X syndrome
Friedreich ataxia

INHERITANCE PROPERTIES
Incomplete penetrance
Variable expression

MODES OF INHERITANCE

TRISOMIES
Nondisjunction
Chromosomal Translocation
Common AUTOSOMAL Trisomies
Trisomy 21 (Down syndrome)
Trisomy 18 (Edward syndrome; 1:8000)
Trisomy 13 (Patau syndrome; 1:15,000)

IMPRINT DISORDERS
Prader-Willi Syndrome
Angelman Syndrome

GENETIC DISORDERS BY CHROMOSOME

Robertsonian translocation
Cri-du-chat syndrome
Williams syndrome

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CLINICAL

COMMON ANALYTES
ELECTROLYTES
RENAL (KIDNEY) FUNCTION TESTS
LIVER FUNCTION TESTS
CARDIAC MARKERS
MINERALS
BLOOD DISORDERS
MISCELLANEOUS

PANEL TESTS

METABOLIC PANEL
BASIC METABOLIC PANEL
COMPREHENSIVE METABOLIC PANEL

SPECIMEN PROCESSING

INSTRUMENTS

SPECIALTIES

ENZYMES AND ISOENZYMES OF CLINICAL IMPORTANCE
ENZYMES
CLINICAL SIGNIFICANCE OF ENZYME ASSAYS 
SERUM ENZYMES IN HEART DISEASES
SERUM ENZYMES IN LIVER DISEASES
SERUM ENZYMES IN GI TRACT DISEASES
SERUM ENZYMES IN MUSCLE DISEASES 
SERUM ENZYMES IN BONE DISEASES
VALUE OF ENZYMES IN MALIGNANCIES
ISOENZYMES

RENAL FUNCTION TESTS
RENAL FUNCTION TESTS
GLOMERULAR FILTRATION TESTS
TESTS FOR RENAL BLOOD FLOW
TESTS OF TUBULAR FUNCTION
OTHER MISCELLANEOUS TESTS TO ASSESS RENAL FUNCTION

LIVER FUNCTION TESTS
FUNCTIONS OF THE LIVER
TESTS BASED ON ABNORMALITIES OF BILE PIGMENT METABOLISM
TESTS BASED ON LIVER’S PART IN CARBOHYDRATE METABOLISM
TESTS BASED ON CHANGES IN PLASMA PROTEINS
TESTS BASED ON ABNORMALITIES OF LIPIDS
TESTS BASED ON THE DETOXICATING FUNCTION OF THE LIVER
TESTS BASED ON EXCRETORY FUNCTION OF LIVER
FORMATION OF PROTHROMBIN BY LIVER
TESTS BASED ON AMINO ACID CATABOLISM 
TESTS BASED ON DRUG METABOLISM
VALUE OF SERUM ENZYMES IN LIVER DISEASES

GASTRIC FUNCTION TESTS
EXAMINATION OF RESTING CONTENTS
FRACTIONAL GASTRIC ANALYSIS: USING TEST MEALS
ACHYLIA GASTRICA
STIMULATION TESTS
SERUM PEPSINOGEN
TUBELESS GASTRIC ANALYSIS

THYROID FUNCTION TESTS
TESTS BASED ON PRIMARY FUNCTION OF THYROID 684
TESTS MEASURING BLOOD LEVELS OF THYROID HORMONES
TESTS BASED ON METABOLIC EFFECTS OF THYROID HORMONES 
THYROID SCANNING 
IMMUNOLOGICAL TESTS FOR THYROID FUNCTIONS *

WATER AND ELECTROLYTE BALANCE AND IMBALANCE
DISTRIBUTION OF BODY WATER AND ELECTROLYTES
DISTRIBUTION OF ELECTROLYTES IN THE BODY
NORMAL WATER BALANCE
NORMAL ELECTROLYTE BALANCE 
REGULATORY MECHANISMS
ABNORMAL WATER AND ELECTROLYTE METABOLISM
DEHYDRATION
PATHOLOGICAL VARIATIONS OF WATER AND ELECTROLYTES
WATER INTOXICATION

ACID BASE BALANCE AND IMBALANCE
ACID-BASE BALANCE IN NORMAL HEALTH 
BUFFERS
ACIDS PRODUCED IN THE BODY
MECHANISMS OF REGULATION OF Ph
ROLE OF DIFFERENT BUFFER SYSTEMS
ROLE OF RESPIRATION IN ACID-BASE REGULATION
RENAL MECHANISMS FOR REGULATION OF ACID-BASE BALANCE
ACID-BASE IMBALANCE 
ACIDOSIS
ALKALOSIS

CEREBROSPINAL FLUID (CSF)—CHEMISTRY AND CLINICAL SIGNIFICANCE
APPEARANCE OF CEREBROSPINAL FLUID
PRESSURE OF CSF
BIOCHEMICAL CHANGES IN CSF
OTHER CHEMICAL CONSTITUENTS 
LANGE COLLOIDAL GOLD REACTION

RADIOACTIVITY: RADIOISOTOPES IN MEDICINE
RADIOACTIVITY 
RADIOISOTOPES
RADIOISOTOPES IN MEDICINE
RADIATION HAZARDS
DIAGNOSTIC AND THERAPEUTIC USES OF RADIOISOTOPES

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TECHNIQUES

SPECTROPHOTOMETRY 
CHROMATOGRAPHY
ELECTROPHORESIS 
PH METRE 
IMMUNOASSAY TECHNIQUES
AUTOMATION IN CLINICAL LABORATORIES

PROTEIN PURIFICATION
DIFFERENT SEPARATION METHODS
Selective precipitation
Gel filtration & preparative gel electrophoresis
Gel electrophoresis and ion-exchange chromatography
Affinity chromatography

PROTEIN ANALYSIS
AMINO ACID COMPOSITION
ion-exchange chromatography
AMINO ACID SEQUENCE
protein must first be broken
Cyanogen bromide - methionine
2-Nitro-5-thiocyanobenezene - cysteine
trypsin - lysine or arginine
chymotrypsin - aromatic - nonpolar
High-performance liquid chromatography (HPLC)
The Edman degradation method
phenylisothiocyanate
Mass spectrometry (MS)
X-RAY CRYSTALLOGRAPHY & NUCLEAR MAGNETIC RESONANCE

DNA-BASED LAB TESTS - DNA ANALYSIS
DNA IN ITS NATIVE STATE MAY BE VERY LARGE - Enzymic digestion
restriction endonucleases - restriction sites
DNA GEL ELECTROPHORESIS
the basis of size
POLYMERASE CHAIN REACTION
Required components
DNA to be amplified
primers
dNTPs
heat-stable DNA polymerase
PCR process
DNA SEQUENCING
KARYOTYPING
FLUORESCENCE IN SITU HYBRIDIZATION
SOUTHERN BLOT(TING)
specific base sequence
SANGER DIDEOXYNUCLEOTIDE METHOD
determine the sequence of bases in DNA fragments
primer
deoxynucleoside triphosphates - DNA polymerase, and a small amount of a different dideoxynucleoside triphosphate (ddNTP)
fluorescent label
automated
DNA FINGERPRINTING
polymorphisms
restriction fragment length polymorphisms (RFLPs)

RNA-BASED LAB TEST
NORTHERN BLOTTING
RNA fragments

PROTEIN-BASED LAB TESTS
PROTEIN GEL ELECTROPHORESIS
WESTERN BLOT
antibodies to detect proteins
ENZYME-LINKED IMMUNOSORBENT ASSAY
IMMUNOHISTOCHEMISTRY
RADIOIMMUNOASSAY

CRISPR/Cas9
Blotting procedures
Southwestern blot
Flow cytometry
Microarrays
Molecular cloning

GENE EXPRESSION MODIFICATIONS
RNA interference
MicroRNA
Small interfering RNA

CLONING OF RECOMBINANT DNA & PROTEIN
chimeric or recombinant DNA

CLINICAL RELEVANCE
DIABETIC SYNDROMES
PITUITARY DWARFISM
HEMATOLOGIC PROBLEMS. RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR

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MISCELLANEOUS

ENVIRONMENTAL BIOCHEMISTRY
LEAD
ARSENIC 
FOOD POLLUTION

BIOCHEMISTRY OF CANCER
BIOCHEMISTRY OF CANCER CELLS AND CARCINOGENESIS
PROPERTIES OF CANCER CELLS 
ETIOLOGY OF CANCER (CARCINOGENESIS) 
EXPERIMENTAL CARCINOGENESIS
GROWTH FACTORS
APOPTOSIS: BIOCHEMISTRY AND ROLE IN CARCINOGENESIS
BIOCHEMISTRY OF METASTASIS
ONCOGENIC MARKERS OR TUMOUR MARKERS
WHAT ARE TUMOUR MARKERS?
CHARACTERISTICS OF AN IDEAL TUMOUR MARKER 
CLINICAL USEFULNESS OF DIFFERENT TUMOUR MARKERS
COMMONLY USED TUMOUR MARKERS
TUMOUR MARKERS NOT USED COMMONLY

BIOPHYSICS: PRINCIPLES AND BIOMEDICAL IMPORTANCE
HYDROGEN ION CONCENTRATION (PH)
BUFFERS
DIFFUSION
OSMOSIS AND OSMOTIC PRESSURE
DIALYSIS
GIBBS-DONNAN MEMBRANE EQUILIBRIUM 
SURFACE TENSION (ST)
VISCOSITY
COLLOIDS

BIOCHEMISTRY OF AGEING
DEFINITION OF AGEING
LIFE SPAN AND LIFE EXPECTANCY 
AGEING THEORIES 
IN SEARCH OF THE SECRETS OF AGEING 
OXYGEN RADICALS
ANTIOXIDANTS AND AGEING GERBILS
GLUCOSE CROSSLINKING
DNA REPAIR
HEAT SHOCK PROTEINS 
HORMONES
HORMONES AND RESEARCH ON AGEING
HORMONE REPLACEMENT
GROWTH FACTORS 
ROLE OF DOPAMINE RECEPTORS IN AGEING 
MACULAR DEGENERATION OF EYE

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COMMON LABORATORY VALUES

TOC
REFERENCES

CONTENTS
DIDACTIC
TOPICS

DIDACTIC

Crowe. Chemistry for the Biosciences: The Essential Concepts. 4e. 2021. [ 776 pages ] [ Amazon ] [ Download ]
Sutton. Chemistry for the life sciences. 2e. 2008. [ 280 pages ] [ Download ] [ Download Chimie pour les étudiants en médecine ] .
Caratini. Encyclopédie & Collection. Médecine. Chimie Organique & Biochimie. 1974. 1985.
Jonsson. Essential chemistry for biochemists. 2017. [ 27 pages ] [ Download ]
https://medicalstudyzone.com/category/chemistry/
https://medicalstudyzone.com/allen-organic-chemistry-handbook-pdf-download/
https://medicalstudyzone.com/category/physics-1/

Fensterbank. Document d’accompagnement de chimie organique. 2007. [ Download ] [ Download ]
Toussaint. Chimie, Biochimie & Biologie Moléculaire. PACES. 2015.

Tellingen. Biochemistry - from a Phenomenological point of view. 1e. 2001. [ 72 pages ] [ Download ]
Le. First Aid USMLE Step 1. Biochemistry. 34e. 2024. 30e. 2020.
Le. First Aid Basic Sciences General Principles. Biochemistry. 3e. 2017.
Salway. Medical Biochemistry at a Glance. 3e. 2012. [ Download ]
Salway. Metabolism at a Glance. 4e. 2017. [ Download ]
Wilcox. HY Biochemistry. 4e. 2009. [ 109 pages ] 
Koolman. Color Atlas of Biochemistry. 3e. 2012. [ 506 pages ]
Abali. LIR Biochemistry. 8e. 2021. 7e. 2017. [ 640 pages ] [ Download 7e ] [ Download 7e ]
Lieberman. BRS Biochemistry, Molecular Biology & Genetics. 7e. 2019. 6e. 2013. 5e. 2009. [ 448 pages ] [ Download 6e ]

Lange Biochemistry Genetics Flashcards [ Download ]
Karandish. Biochemistry Map (Lippincott's MedMaps).1e. 2010.
Ahern. kevingahern.com - kevingahern.com/biochemistry-resources - powerpoint-files [ Teaching Powerpoint Files ]
Ahern. Biochemistry Free and Easy. V3.0. 2013. [ 823 pages ] [ Download ]
Ahern. Biochemistry Free For All. V1.2. 2017. [ 3548 pages ] [ Download ]
Mathews. Biochemistry. 4e. [ 1377 pages ] [ Download ] [ Amazon ]
Gerhard. Biochemical Pathways : An Atlas of Biochemistry and Molecar Biology 2e. 2012. [ biochemical-pathways.com ]
Pelley. Rapid Review Biochemistry. 3e. 2010. [ Download ]
Janson. Big Picture Medical Biochemistry.1e. 2012.
https://medicostimes.com/mn-chatterjea-biochemistry-pdf/
https://awesomechem.wordpress.com/wp-content/uploads/2016/10/harpers-illustrated-biochemistry-28th-ed-robert-k-murray-et-al-mcgraw-hill-2009.pdf

Lavoinne. Aide-mémoire de biochimie et biologie moléculaire. 6e. 2008. [ Lipides Structure V1 PDF ] [ 1990 Kamoun 4e Download Beaux Schémas Explicatifs ! ]
Hecketsweiler. Voyage en biochimie : Circuits en biochimie humaine, nutritionnelle et métabolique. 3e. 2006. [ Download ] [ Carte Nutrionnelle et Métabolique Download  ]
Caratini. Panorama Sciences. Biologie. Biochimie. 1993.

Interrelazioni tra le diverse vie metaboliche [ Download PDF ] [ Download JPG ]

TOPICS

OVERVIEW
https://en.wikipedia.org/wiki/Outline_of_biochemistry

CHEMISTRY
https://www.amazon.co.uk/Essential-Chemistry-Biochemistry-Revised-DPhil/dp/B001CDHKQQ
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869253/
https://www.studocu.com/en-au/document/australian-national-university/biochemistry-and-nutrition/chemistry-for-biochemistry/2699271

BIOMOLECULES
https://en.wikipedia.org/wiki/Biomolecule
https://en.wikipedia.org/wiki/Cofactor_(biochemistry)

ENZYMES
https://en.wikipedia.org/wiki/Enzyme

METABOLISM
https://en.wikipedia.org/wiki/Metabolism
https://ib.bioninja.com.au/standard-level/topic-4-ecology/41-species-communities-and/types-of-metabolism.htm
https://www.researchgate.net/figure/Classification-of-organisms-based-on-their-primary-source-of-energy-reveals-the-metabolic_fig1_228719691

MOLECULAR BIOLOGY
https://en.wikipedia.org/wiki/Molecular_biology

CLINICAL
https://en.wikipedia.org/wiki/Clinical_chemistry
https://archive.org/details/tietzfundamental0000unse_o4o0
https://fr.wikipedia.org/wiki/Biochimie_clinique
https://it.wikipedia.org/wiki/Chimica_clinica

PLANT

DOWNLOAD
https://medicostimes.com/biochemistry/

UNSORTED
medicostimes.com/satyanarayana-biochemistry-pdf/
iubmb-nicholson.org/pdf/MetabolicPathways_6_17_04_.pdf
genome.jp/kegg/pathway.html
iubmb-nicholson.org/index
songkhlastation.com/download/stryersc2.pdf
http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/General_Information/metabolic_pathways_poster.pdf
http://www.kegg.jp/
http://www.dmoz.org/Science/Biology/Biochemistry_and_Molecular_Biology
http://www.garlandscience.com/product/isbn/9780815341055
http://www.garlandscience.com/garlandscience_resources/book_resources.jsf?chapter=ALL_CHAPTERS
http://www.amazon.com/Molecular-Biology-Cell-Bruce-Alberts/dp/0815341059
http://en.wikipedia.org/wiki/Molecular_Biology_of_the_Cell_(textbook)
http://www.ncbi.nlm.nih.gov/books/NBK21054/
http://emboj.embopress.org/
http://emboj.embopress.org/collection/neuroscience
http://www.molbiolcell.org/
http://www.biomedcentral.com/bmcmolbiol
http://molbio.princeton.edu/
http://www.nature.com/scitable/ebooks/cntNm-16553173
https://www.youtube.com/watch?v=J3HVVi2k2No

https://www.sciencedirect.com/science/article/pii/S1550413121005337

https://www.amazon.com/Biochemistry-Quick-Study-Academic-BarCharts/dp/1423208536/

https://migration.wordpress.com/wp-content/uploads/2007/08/signal-transduction.jpg

AMINO ACIDS
CARBOHYDRATE STRUCTURE
CHEMISTRY WATER BUFFERS
CITRIC ACID CYCLE
DNA REPLICATION REPAIR RECOMBINATION
ENZYME MECHANISM
ENZYME REGULATION
ENZYMES
ETS & OXIDATIVE PHOSPHORYLATION
FATTY ACID METABOLISM
GENE EXPRESSION
GLYCOGEN METABOLISM
GLYCOLYSIS
HEMOGLOBIN
INTRODUCTION
LIPID METABOLISM
LIPIDS & MEMBRANES
MEMBRANE TRANSPORT
METABOLIC ENERGY
NITROGEN METABOLISM
NUCLEOTIDE METABOLISM
PROTEIN CHARACTERIZATION
PROTEIN STRUCTURE
SIGNALING
TRANSCRIPTION
TRANSLATION

SEE ALSO CHEMISTRY

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