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Textbook of Biochemistry for Medical Students
DM Vasudevan, Sreekumari S
SECTION A: CHEMICAL BASIS OF LIFE
CHAPTER 1:
Biochemical Perspective to Medicine
BIOMOLECULES
STUDY OF METABOLIC PROCESSES
STABILISING FORCES IN MOLECULES
WATER; THE UNIVERSAL SOLVENT
PRINCIPLES OF THERMODYNAMICS
DONNAN MEMBRANE EQUILIBRIUM
CHAPTER 2:
Subcellular Organelles and Cell Membranes
SUBCELLULAR ORGANELLES
NUCLEUS
ENDOPLASMIC RETICULUM (ER)
GOLGI APPARATUS
LYSOSOMES
PEROXISOMES
MITOCHONDRIA
PLASMA MEMBRANE
TRANSPORT MECHANISMS
1-A. Simple Diffusion
1-B. Facilitated Diffusion
Aquaporins
1-C. Ion Channels
Ligand gated channels
Voltage Gated Channels
Ionophores
2. Active Transport
2-A. Sodium pump
Clinical Applications
2-B. Calcium Pump
Uniport, Symport and Antiport
Clinical Applications
CHAPTER 3:
Amino Acids: Structure and Properties
CLASSIFICATION OF AMINO ACIDS
1. Based on Structure
Special Groups in Amino Acids
2. CLASSIFICATION BASED ON SIDE CHAIN
3. CLASSIFICATION BASED ON METABOLISM
4. CLASSIFICATION BASED ON NUTRITIONAL REQUIREMENTS
PROPERTIES OF AMINO ACIDS
B. Optical Activity
GENERAL REACTIONS OF AMINO ACIDS
A. Due to Carboxyl Group
1. Decarboxylation
2. Amide Formation
B. Reactions due to Amino Group
3. Transamination
4. Oxidative Deamination
5. Formation of Carbamino Compound
C. Reactions due to Side Chains
6. Transmethylation
7. Ester Formation by the OH Group
8. Reaction of the Amide Group
9. Reactions of SH Group
Amino Acid Derivatives of Importance
PEPTIDE BOND FORMATION
CHAPTER 4:
Proteins: Structure and Function
STRUCTURE OF PROTEINS (Organisation of Proteins)
1. Primary Structure
1-A. Sequence of amino acids in proteins
1-B. Characteristics of a Peptide Bond
1-C. Numbering of Amino Acids in Proteins
1-D. Branched and Circular Proteins
1-E. Primary Structure of Insulin
1-F. Pro-insulin
1-G. Primary Structure Determines Biological Activity
2. Secondary Structure of Proteins
2-A. Alpha helix
2-B. Beta-pleated sheet
2-C. Collagen helix
3. Tertiary Structure
4. Quaternary Structure
Structure–Function Relationship
Enzymes
Transport Proteins
Structural Proteins
STUDY OF PROTEIN STRUCTURE
PHYSICAL PROPERTIES OF PROTEINS
PRECIPITATION REACTIONS OF PROTEINS
CLASSIFICATION OF PROTEINS
A. Classification based on Functions
B. Classification based on Composition and Solubility
B-1. Simple Proteins
B-2. Conjugated Proteins
B-3. Derived Proteins
C. Classification based on the Shape
C-1. Globular proteins
C-2. Fibrous proteins
D. Classification based on Nutritional Value
D-1. Nutritionally rich proteins
D-2. Incomplete Proteins
D-3. Poor Proteins
Biologically Important Peptides
QUANTITATIVE ESTIMATION
CHAPTER 5:
Enzymology: General Concepts and Enzyme Kinetics
CLASSIFICATION OF ENZYMES
CO-ENZYMES
MODE OF ACTION OF ENZYMES
MICHAELIS-MENTEN THEORY
FISCHER'S TEMPLATE THEORY
KOSHLAND'S INDUCED FIT THEORY
ACTIVE SITE OR ACTIVE CENTRE OF ENZYME
THERMODYNAMIC CONSIDERATIONS
ENZYME KINETICS
FACTORS INFLUENCING ENZYME ACTIVITY
1. Enzyme Concentration
2. Effect of Substrate Concentration
2-A. Michaelis Constant
2-B. Definition of Km
2-C. Double Reciprocal Plot
2-D. Co-operative Binding
3. Effect of Concentration of Products
4. Effect of Temperature
5. Effect of pH
6. Enzyme Activation
7. Enzyme Inhibition
7-A. Competitive Inhibition
Clinical Significance of Competitive Inhibition
7-B. Non-competitive Inhibition (Irreversible)
7-C. Uncompetitive Inhibition
7-D. Suicide Inhibition
7-E. Allosteric Regulation
Salient Features of Allosteric regulation
7-F. Key enzymes
7-G. Feedback Inhibition
8-A. Induction
8-B. Repression
9. Covalent Modification
SPECIFICITY OF ENZYMES
CHAPTER 6:
Iso-enzymes and Clinical Enzymology
ISO-ENZYMES
CLINICAL ENZYMOLOGY
LACTATE DEHYDROGENASE (LDH) (LD)
CREATINE KINASE (CK)
CARDIAC TROPONINS (CTI/CTT)
ASPARTATE AMINO TRANSFERASE (AST)
Markers for cardiac diseases
ALANINE AMINO TRANSFERASE (ALT)
ALKALINE PHOSPHATASE (ALP)
Nucleotide Phosphatase (NTP)
Gamma Glutamyl Transferase (GGT)
Enzyme Profile in Liver Diseases
ACID PHOSPHATASE (ACP)
PROSTATE SPECIFIC ANTIGEN (PSA)
Cholinesterase (ChE)
GLUCOSE-6-PHOSPHATE DEHYDROGENASE
AMYLASE
LIPASE
ENOLASE
Enzymes as Therapeutic Agents
Enzymes Used for Diagnosis
Immobilised Enzymes
CHAPTER 7:
Chemistry of Carbohydrates
NOMENCLATURE
STEREOISOMERS
Reference Carbon Atom of Sugars
D and L isomerism of Glucose
Optical Activity
1. Diastereo-isomers of Glucose
2. Epimerism of Aldoses
3. Anomerism of Sugars
Three Representations of Glucose Structure
Fructose is a Ketohexose
REACTIONS OF MONOSACCHARIDES
Amino Sugars
Deoxy Sugars
Pentoses
DISACCHARIDES
Sucrose
Lactose
Maltose
Isomaltose
POLYSACCHARIDES
1. Starch
A. Structure of starch
B. Hydrolysis of Starch
C. Action of Amylases on Starch
2. Glycogen
3. Cellulose
4. Inulin
5. Dextrans
6. Chitin
HETEROGLYCANS
Agar
MUCOPOLYSACCHARIDES
GLYCOPROTEINS AND MUCOPROTEINS
CHAPTER 8:
Chemistry of Lipids
CLASSIFICATION OF LIPIDS
FATTY ACIDS
SATURATED FATTY ACIDS
UNSATURATED FATTY ACIDS
Properties of Fatty Acids
1. Hydrogenation
2. Halogenation
3. Melting point
4. Salt formation
5. Ester formation
6. Oxidation of Fatty Acids
NEUTRAL FATS
PHOSPHOLIPIDS
1. Phosphatidyl choline or Lecithin
Action of Phospholipases
2. Phosphatidyl ethanolamine or Cephalin
3. Phosphatidyl inositol
4. Plasmalogens
5. Phosphatidyl glycerol
6. Sphingolipids
7. Phosphosphingosides
Non-phosphorylated Lipids
Glycosphingolipids (Glycolipids)
Gangliosides
Sulfolipids or Sulfatides
SECTION B: GENERAL METABOLISM
CHAPTER 9:
MAJOR METABOLIC PATHWAYS OF GLUCOSE
EXPERIMENTAL STUDY OF METABOLISM
METABOLISM
DIGESTION OF CARBOHYDRATES
ABSORPTION OF CARBOHYDRATES
Absorption of Glucose
1. Co-transport from Lumen to Intestinal Cell
2. Another Uniport System Releases Glucose into Blood
3. Glucose Transporter 4
GLUCOSE METABOLISM
GLYCOLYSIS (EMBDEN-MEYERHOF PATHWAY)
Steps of Glycolytic Pathway.
Step 1 of Glycolysis (Fig. 9.5)
Step 2 of Glycolysis
Step 3 of Glycolysis
Step 4 of Glycolysis
Step 4-A of Glycolysis
Step 5 of Glycolysis
Step 6 of Glycolysis
Step 7 of Glycolysis
Step 8 of Glycolysis
Step 9 of Glycolysis
Step 10 of Glycolysis
Significance of Lactate Production
Steps 5 and 10 are Coupled
Energy Yield from Glycolysis
Regulation of Glycolysis
Factors Regulating Glycolysis
CORI'S CYCLE OR LACTIC ACID CYCLE
Pasteur Effect
Rapaport Leubering Cycle (BPG Shunt)
Significance of BPG
METABOLIC FATE OF PYRUVATE
GLUCONEOGENESIS
1. Definition
2. Site
3. Key gluconeogenic enzymes
1. Pyruvate carboxylase reaction
Malate Aspartate Shuttle
2. Phosphoenol pyruvate carboxy kinase
Partial Reversal of Glycolysis
3. Fructose-1,6-bisphosphatase
4. Glucose-6-phosphatase Reaction
Significance of Gluconeogenesis
Substrates for Gluconeogenesis
1. Lactate
2. Glucogenic amino acids
2-A. Glucose-Alanine Cycle
3. Glycerol
4. Propionyl CoA
Regulation of Gluconeogenesis
1. Pyruvate Carboxylase
2. Fructose-1,6-bisphosphatase
3. ATP
4. Hormonal Regulation of Gluconeogenesis
Clinical Significance of Pyruvate Metabolism
GN ratio or DN ratio
GLYCOGEN METABOLISM
DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS)
GLYCOGEN SYNTHESIS (GLYCOGENESIS)
Regulation of Glycogen Metabolism
2. Generation of Cyclic AMP (cAMP)
2-A. Protein Kinase Activation
2-B. Phosphorylase Kinase Activation
3. Glycogen Phosphorylase in Liver and Muscle
4. Glycogen Synthase
5. Summary of Regulation
GLYCOGEN STORAGE DISEASES
CHAPTER 10:
Regulation of Blood Sugar; Insulin and Diabetes Mellitus
REGULATION OF BLOOD GLUCOSE
Factors Maintaining Blood Sugar
Post-prandial Regulation
Regulation in Fasting State
NORMAL PLASMA GLUCOSE LEVEL
Effects of Hormones on Glucose Level in Blood
A. Effect of Insulin (hypoglycemic hormone)
B. Glucagon (hyperglycemic hormone)
C. Cortisol (hyperglycemic hormone)
D. Epinephrine or Adrenaline (hyperglycemic)
E. Growth Hormone (hyperglycemic)
Determination of Glucose in Body Fluids
Enzymatic Method
Effect of Food on Glucose Level
ORAL GLUCOSE TOLERANCE TEST (OGTT)
Normal Values and Interpretations
Diagnostic Criteria for Diabetes Mellitus
Causes for Abnormal GTT Curve
1. Impaired Glucose Tolerance (IGT)
2. Impaired Fasting Glycemia (IFG)
3. Gestational Diabetes Mellitus (GDM)
4. Alimentary Glucosuria
5. Renal Glucosuria
Factors Affecting GTT
Corticosteroid Stressed GTT
REDUCING SUBSTANCES IN URINE
Differential Diagnosis of Reducing Substances in Urine
1. Hyperglycemic glucosuria
2. Fructosuria
3. Lactosuria
4. Galactosuria
5. Pentosuria
6. Non-carbohydrate Reducing Compounds
Identification of Reducing Sugars
Benedict's Test
INSULIN
Factors Increasing Insulin Secretion
1. Glucose
2. Gastrointestinal hormones
Factors decreasing the insulin secretion
Degradation of insulin
Mechanisms of Action of Insulin
1. Insulin Receptors
2. Signal Transduction
3. Gene Transcription (new enzyme synthesis)
4. Activation of Enzymes
5. DNA Synthesis
6. Glucose uptake
Physiological Actions of Insulin (Metabolic Effects of Insulin)
1. Uptake of Glucose by Tissues
2. Utilisation of Glucose
3. Hypoglycemic Effect
4. Lipogenesis
5. Anti-lipolytic Effect
6. Anti-ketogenic Effect
7. Other General Effects
HYPERGLYCEMIC HORMONES
GLUCAGON
Other Anti-insulin Hormones
Diabetes mellitus
1. Type 1 Diabetes Mellitus
2. Type 2 Diabetes Mellitus
3. Diabetic prone states:
4. Secondary to other known causes:
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Metabolic Syndrome
Metabolic Derangements in Diabetes
1. Derangements in Carbohydrate Metabolism
2. Derangements in Lipid Metabolism
3. Derangement in Protein Metabolism
Clinical Presentations in Diabetes Mellitus
Cardinal Symptoms
Acute Metabolic Complications
Chronic Complications of Diabetes Mellitus
Laboratory Investigations in Diabetes
1. Blood glucose level
2. Complete lipid profile
3. Kidney function tests
4. Micro-albuminuria and frank albuminuria
5. Glycated Hemoglobin
Interpretation of Glyco-Hb Values
7. Other Glycated Proteins (Fructosamines)
Management of Diabetes Mellitus
Hypoglycemia
CHAPTER 11:
Minor Metabolic Pathways of Carbohydrates
HEXOSE MONOPHOSPHATE (HMP) SHUNT PATHWAY
A. Oxidative Phase
Step 1 of HMP Pathway
Step 2 of HMP Pathway
Step 3, NADPH is again Generated
B. Non-Oxidative Phase
Step 4: Isomerisation
Step 5: Transketolase Reaction
Step 6: Transaldolase Reaction
Step 7: Second Transketolase Reaction
Step 8: Regeneration of Glucose-6-Phosphate
Regulation of HMP Shunt Pathway
Summary of Shunt Pathway
Physiological Significance of the Pathway
1. Pathway is operating in following organs:
2. Generation of Reducing Equivalents
3. Free Radical Scavenging
4. Erythrocyte Membrane Integrity
5. Prevention of Met-Hemoglobinemia
6. Detoxification of Drugs
7. Lens of Eye
8. Macrophage bactericidal activity
9. Availability of Ribose
10. What about ATP?
Clinical Significance of Shunt pathway
1. GPD deficiency
2. Met-hemoglobinemia
3. Thiamine Deficiency
GLUCURONIC ACID PATHWAY OF GLUCOSE
Essential Pentosuria
POLYOL PATHWAY OF GLUCOSE
FRUCTOSE METABOLISM
GALACTOSE METABOLISM
METABOLISM OF ALCOHOL
Biochemical Alterations in Alcoholism
Chronic Alcoholism
A. Alcoholism and liver
B. Alcoholism and Nervous System
C. Alcohol and Cardiovascular System
D. Laboratory findings in chronic alcoholism
METABOLISM OF AMINO SUGARS
GLYCOPROTEINS
Mucopolysaccharidoses
CHAPTER 12:
Metabolism of Fatty Acids
DIGESTION OF LIPIDS
ABSORPTION OF LIPIDS
Absorption of Long Chain Fatty Acids
1. Mixed micelle formation
2. Enterohepatic Circulation of Bile Salts
3. Re-esterification Inside the Mucosal Cell
3. Chylomicrons
4. SCFA Absorption is Different
5. Abnormalities in Absorption of Lipids
6. Fate of Chylomicrons
BETA OXIDATION OF FATTY ACIDS
Preparative steps for beta oxidation
Preparative step 1: Activation of Fatty Acids
Preparative step 2: Role of Carnitine
Preparative step-3: Carnitine Acyl Transferase
Preparative step-4: Translocase
Clinical Applications
Beta oxidation steps
Step 1: FAD Linked Dehydrogenase
Step 2: Hydration
Step 3: NAD+ Dependent Dehydrogenase
Step 4: Cleavage
Further Cycles
Energetics of Beta Oxidation (ATP Yield)
Regulation of Beta Oxidation
Defects in Beta Oxidation
Organic Acidurias
OXIDATION OF ODD CHAIN FATTY ACIDS
Alpha Oxidation
Refsum's Disease
Infantile Refsum's Disease
Omega Oxidation
DE NOVO SYNTHESIS OF FATTY ACIDS
Fatty Acid Synthase (FAS) Complex
Advantages of Multi-enzyme Complex
1st domain or condensing unit
2nd domain or reduction unit
3rd domain or releasing unit
Step 1: Carboxylation of Acetyl CoA
Step 2: Three C and Two C Units are Added
Step 3: Condensation
Step 4: Reduction
Step 5: Dehydration
Step 6: Second Reduction
Cycling of Reactions
Step 7: Palmitic acid is released
Summary of de-novo Synthesis
Co-enzymes of Fatty Acid Synthesis
1. Pentose phosphate pathway
2. Malic enzyme
Regulation of Fatty Acid Synthesis
1. Availability of substrates:
2. Acetyl CoA Carboxylase
3. Insulin Favours Lipogenesis
4. Glucagon inhibits Lipogenesis
SYNTHESIS OF TRIGLYCERIDES (TAG)
METABOLISM OF ADIPOSE TISSUE
Adipokines
Liver–Adipose Tissue Axis
FATTY LIVER AND LIPOTROPIC FACTORS
Lipotropic Factors
METABOLISM OF KETONE BODIES
A. Ketogenesis
Step 1. Condensation
Step 2. Production of HMG CoA
Step 3. Lysis
Step 4. Reduction
Step 5. Spontaneous decarboxylation
B. Ketolysis
KETOSIS
Causes for Ketosis
Explanation for Ketogenesis
Level 1: Lipolysis
Level 2: Entry of Fatty Acid to Mitochondria
Level 3: Oxidation of Acetyl CoA
Consequences of Ketosis
Diagnosis of Ketosis
Differential Diagnosis of Ketosis
Management of Ketoacidosis
CHAPTER 13:
Cholesterol, Lipoproteins and Cardiovascular Diseases
BIOSYNTHESIS OF CHOLESTEROL
PLASMA LIPIDS
Classification of Lipoproteins
General Characteristics of Lipoproteins
Separation by Ultracentrifugation
Separation by Electrophoresis
Apo-lipoproteins
1. CHYLOMICRONS
2. VERY LOW DENSITY LIPOPROTEINS
3. LOW DENSITY LIPOPROTEINS (LDL)
4. HIGH DENSITY LIPOPROTEIN (HDL)
5. FREE FATTY ACID (FFA)
HYPOLIPOPROTEINEMIAS
HYPERLIPIDEMIAS
ATHEROSCLEROSIS
Plasma LIPID PROFILE
RISK FACTORS FOR ATHEROSCLEROSIS
PREVENTION OF ATHEROSCLEROSIS
FORMATION OF BILE ACIDS
CHAPTER 14:
MCFA, PUFA, Prostaglandins and Compound Lipids
MONO UNSATURATED FATTY ACIDS (MUFA)
POLY UNSATURATED FATTY ACIDS (PUFA)
EICOSANOIDS
PROSTAGLANDINS (PGs)
Biological Actions and Clinical Applications
1. Effects on CVS
2. Effects on Ovary and Uterus
3. Effects on Respiratory Tract
4. Effects on Immunity and Inflammation
5. Effects on Gastrointestinal Tract
6. Metabolic Effects
Leukotrienes (LTs)
Synthesis of compound Lipids
Glycerophosphatides
Phosphatidyl Inositol Synthesis
Synthesis of Phosphatidyl Choline
Synthesis of Sphingolipids
Synthesis of Ceramide
Synthesis of Sphingomyelin
Niemann Pick's Disease
Synthesis of Glycosphingolipids
Synthesis of Cerebrosides
Gaucher's disease
Synthesis of Sulfatides
Synthesis of Gangliosides
Tay-Sachs Disease
LIPID STORAGE DISEASES
CHAPTER 15:
Amino Acid Metabolism, General (Urea Cycle, One Carbon Metabolism)
DIGESTION OF PROTEINS
A. Gastric Digestion of Proteins
1. Rennin
2. Pepsin
B. Pancreatic Digestion of Proteins
3. Trypsin
4. Chymotrypsin
5. Carboxypeptidases
C. Intestinal Digestion of Proteins
6. Leucine aminopeptidase
7. Proline amino peptidase
8. Dipeptidases and tripeptidases
ABSORPTION OF AMINO ACIDS
Intracellular Protein Degradation
Cathepsins, Ubiquitin and Proteasomes
Inter-organ Transport of Amino Acids
In fasting state
In the fed state
GENERAL METABOLISM OF AMINO ACIDS
FORMATION OF AMMONIA
A. Transamination
Biological Significance of Transamination
1. First step of catabolism
2. Synthesis of non-essential amino acids
3. Interconversion of amino acids
Exceptions
Clinical Significance of Transamination
B. Transdeamination
Oxidative Deamination of Glutamate
Minor Pathways of Deamination
Nonoxidative Deaminations
DISPOSAL/DETOXIFICATION OF AMMONIA
UREA CYCLE
Regulation of the Urea Cycle
1. Coarse Regulation
2. Fine Regulation
3. Compartmentalisation
Disorders of Urea Cycle
Hepatic Coma (Acquired Hyperammonemia)
Urea Level in Blood
ONE-CARBON METABOLISM
CHAPTER 16:
Simple, Hydroxy and Sulphur Containing Amino Acids (Glycine, Serine, Methionine, Cysteine)
GLYCINE (GLY) (G)
Utilisation of Glycine
1. Glycine cleavage system
2. Glucogenic Pathway
3. Special Metabolic Functions of Glycine
4. Creatine and Creatine Phosphate
5. Synthesis of Heme
6. Synthesis of Purines
7. Synthesis of Glutathione
8. Glycine as a Conjugating Agent
9. Glycine as a Neurotransmitter
10. Glycine as a Constituent of Protein
Metabolic Errors in Relation to Glycine
1. Nonketotic hyperglycinemia
2. Primary Hyperoxaluria
Catabolism of Serine
Metabolic Functions of Serine
7. Choline synthesis:
8. Selenocysteine
9. Serine as a Component of Protein
ALANINE (Ala) (A)
Metabolic Functions of Cysteine
1. Formation of Glutathione
2. Amino Acid Transport
3. Co-enzyme Role
4. RBC Membrane Integrity
5. Met-hemoglobin
6. Conjugation for Detoxification
7. Activation of Enzymes
8. Formation of Taurine
9. Keeping the Correct Structure of Proteins
Metabolism of Sulphur
Formation of Active Sulfate
Cystinuria
Cyanide-nitroprusside Test
Cystinosis
Hyper-methioninemias
HOMOCYSTINURIAS
CHAPTER 17:
Acidic, Basic and Branched Chain Amino Acids (Glutamic acid, Aspartic acid, Lysine, Arginine, Nitric oxide, Valine, Leucine, Isoleucine)
NITRIC OXIDE (NO)
POLYAMINES
Biogenic Amines
BRANCHED CHAIN AMINO ACIDS
Isovaleric Aciduria
CHAPTER 18:
Aromatic Amino Acids (Phenylalanine, Tyrosine, Tryptophan)
PHENYLKETONURIA (PKU)
ALKAPTONURIA
ALBINISM
HYPERTYROSINEMIAS
Serotonin
Functions of Serotonin
Catabolism of Serotonin
Carcinoid Tumors
Melatonin
Putrefaction of Tryptophan
Hartnup's Disease
Histamine
Histidinemia
Folic Acid Deficiency
FIGLU excretion test
PROLINE (Pro) (P)
AMINO ACIDURIAS
CHAPTER 19:
Citric Acid Cycle (Integration of metabolism; adaptation to starvation)
METABOLIC PROFILE OF ORGANS
1. Brain
2. Skeletal Muscle
3. Adipose Tissue
4. Liver
Metabolic Adaptations During Starvation
First Stage: Glycogenolysis
Second Stage: Gluconeogenesis
Third Stage: Lipolysis
Fourth Stage: Acidosis
Fifth stage: Death from starvation
CHAPTER 20:
Biological Oxidation and Electron Transport Chain
BIOLOGICAL OXIDATION
Electron Transport Chain
Energetics of Oxidative Phosphorylation
ENZYMES AND CO-ENZYMES
HIGH ENERGY COMPOUNDS
Adenosine Triphosphate (ATP)
Structure of Mitochondria
ORGANISATION OF ET CHAIN
Chemi-osmotic Theory
Proton Pump and ATP Synthesis
ATP Synthase (5th Complex)
Binding Change Mechanism
Regulation of ATP Synthesis
Inhibitors of ATP Synthesis
Diseases Associated with Mitochondrial System
SECTION C: PROTEINS OF PLASMA AND TISSUES
CHAPTER 21:
Plasma proteins
ELECTROPHORESIS
ALBUMIN
Functions of Albumin
1. Colloid Osmotic Pressure of Plasma
2. Transport Function
3. Buffering Action
4. Nutritional Function
Clinical Applications
1. Blood-Brain Barrier
2. Drug Interactions
3. Protein-Bound Calcium
4. Therapeutic Use
5. Edema
6. Normal Value
7. Hypo-albuminemia
Albumin-Globulin Ratio
Hypoproteinemia
Hyper-gamma-globulinemias
1. Low Albumin Level
2. Chronic Infections
3. Multiple Myeloma
TRANSPORT PROTEINS
Polymorphism
ACUTE PHASE PROTEINS
Negative Acute Phase Proteins
CLOTTING FACTORS
Fibrinolysis
Clinical Significance
ABNORMALITIES IN COAGULATION
CHAPTER 22:
Immunochemistry
STRUCTURE OF IMMUNOGLOBULINS
Different Classes of Immunoglobulins
1. lmmunoglobulin G (IgG)
2. Immunoglobulin M (IgM)
3. Immunoglobulin A (IgA)
4. Immunoglobulin E (IgE)
PARAPROTEINEMIAS
COMPLEMENT SYSTEM
PRIMARY AND SECONDARY IMMUNE RESPONSES
Transposition of Genes
Gene, Cistron, Split Gene, Polypeptide
Molecular Structure of Antigens
Soluble Factors
1. Interleukins (IL)
2. Interferons (IFN)
3. Macrophage Migration Inhibition Factor
CHAPTER 23:
Tissue Proteins in Health and Disease
COLLAGEN
Abnormalities in Collagen
1. Osteogenesis Imperfecta
2. Ehlers-Danlos Syndrome
3. Homocystinuria
4. Marfan's Syndrome
5. Deficiency of Ascorbic Acid
6. Lathyrism
ELASTIN
Keratins
MUSCLE PROTEINS
LENS PROTEINS
PRIONS
Prion Proteins : Abnormal Tertiary Structure
Abnormal Proteins can be Infectious
Pathogenesis of Prion Diseases
Human Prion Diseases
Prion Diseases in Animals
Alzheimer's Disease (AD)
Molecular Defects in AD
CHAPTER 24:
Heme Synthesis and Breakdown
FUNCTION OF HEME
Biosynthesis of Heme
Step 1: ALA synthesis
Step 2: Formation of PBG
Step 3: Formation of UPG
Step 4: Synthesis of CPG
Step 5: Synthesis of PPG
Step 6: Generation of PP
Step 7: Generation of Heme
Regulation of Heme Synthesis
Shunt Bilirubin
Disorders of Heme Synthesis
Acute Intermittent Porphyria (AIP)
Congenital Erythropoietic Porphyria
Diagnosis of Porphyrias
Acquired Porphyrias
CATABOLISM OF HEME
Plasma Bilirubin
Van den Bergh Test for Bilirubin
Tests for Bile Pigments
HYPERBILIRUBINEMIAS
1. Congenital Hyperbilirubinemias
1-A. Crigler-Najjar Syndrome
1-B. Gilbert's Disease
1-C. Dubin Johnson's Syndrome
1-D. Rotor Syndrome
2. Acquired Hyperbilirubinemias
2-A. Physiological Jaundice
2-B. Breast Milk Jaundice
3. Hemolytic Jaundice
3-A. Hemolytic Disease of the Newborn
3-B. Hemolytic Diseases of Adults
4. Hepatocellular Jaundice
5. Obstructive Jaundice
CHAPTER 25:
Hemoglobin (Structure, Oxygen and Carbon Dioxide Transport, Abnormal Hemoglobins)
STRUCTURE Of HEMOGLOBIN
TRANSPORT OF OXYGEN BY HEMOGLOBIN
Oxygen Dissociation Curve (ODC)
1. Heme-heme Interaction and Co-operativity
2. Effect of pH and pCO2
3. The Bohr Effect
4. The Chloride Shift
5. Effect of Temperature
6. Effect of 2,3-BPG
Laboratory Diagnosis
TRANSPORT OF CARBON DIOXIDE
Fetal Hemoglobin (HbF)
Hemoglobin A2
HEMOGLOBIN DERIVATIVES
1. Carboxy-Hemoglobin (Carbon Monoxy Hb) (CO-Hb)
2. Met-hemoglobin (Met-Hb)
2-A. Met-hemoglobinemias
2-B. Congenital Met-hemoglobinemia
2-C. Acquired or Toxic Met-hemoglobinemia
2-D. Laboratory analysis
3. Hemin Crystals
4. Sulf-hemoglobinemia
HEMOGLOBIN (GLOBIN CHAIN) VARIANTS
Hemoglobinopathies
1. Sickle syndromes
2. Unstable hemoglobins
3. Hemoglobins with abnormal oxygen affinity
4. Structural variations leading to thalassemia
5. Non-symptomatic hemoglobin variants
1. Hemoglobin S (HbS)
(Sickle Cell Hemoglobin)
1-A. Sickle Cell Disease
1-B. Sickle Cell Trait
1-C. Electrophoresis
1-D. Sickling Test
1-E. Management of Sickle Cell Disease
2. Hemoglobin E
3. Hemoglobin C
4. Hemoglobin D
5. M-Hemoglobins (Hb M)
6. Inheritance of Hemoglobin Variants
THALASSEMIAS
2. Alpha thalassemias
3. Thalassemia Syndromes
4. Hemoglobin Lepore
Myoglobin (Mb)
ANEMIAS
SECTION D: NUTRITION
CHAPTER 26:
Fat Soluble Vitamins (A, D, E, K)
CHAPTER 27:
Water Soluble Vitamins
CHAPTER 28:
Mineral Metabolism
CHAPTER 29:
Energy Metabolism and Nutrition
NUTRITIONAL IMPORTANCE OF LIPIDS
IMPORTANCE OF PROTEINS
PROTEIN–ENERGY MALNUTRITION
OBESITY
PRESCRIPTION OF DIET
CHAPTER 30:
Detoxification and Biotransformation of Xenobiotics
PHASE ONE REACTIONS
PHASE TWO REACTIONS; CONJUGATIONS
2. Sulfate conjugation
3. Cysteine and Glutathione
4. Acetylation
5. Conjugation with Glycine
6. Conjugation with Glutamine
7. Methylation Reactions
PHASE THREE REACTIONS
CHAPTER 31:
Environmental Pollution and Heavy Metal Poison
CORROSIVES
Cyanide Poisoning
IRRITANTS
HEAVY METAL POISONS
1. Lead Poisoning
1-A. Sources of lead poison
1-B. Signs and Symptoms of Lead Poisoning
1-C. Treatment of Lead Poisoning
2. Mercury Poisoning
2-A. Elemental mercury
2-B. Inorganic Mercury
2-C. Organic Mercury
3. Aluminium Toxicity
4. Arsenic Toxicity
PESTICIDES AND INSECTICIDES
OCCUPATIONAL AND INDUSTRIAL HAZARDS
AIR POLLUTANTS
TOXIC SUBSTANCES IN FOODSTUFFS
CHAPTER 32:
Free Radicals and Anti-oxidants
CLINICAL SIGNIFICANCE
Lipid Peroxidation
1. Initiation Phase
2. Propagation Phase
3. Termination Phase
Role of Anti-oxidants
Anti-oxidants
Anti-oxidants used as therapeutic agents
Commercial Use of Anti-oxidants
Related Topics
SECTION E: HOMEOSTASIS MECHANISMS
CHAPTER 33:
Acid-base Balance and pH
ACIDS AND BASES
BUFFERS
ACID–BASE BALANCE
1. BUFFERS OF THE BODY FLUIDS
2. RESPIRATORY REGULATION OF pH
3. RENAL REGULATION OF pH
CELLULAR BUFFERS
DISTURBANCES IN ACID–BASE BALANCE
Classification of Acid-Base Disturbances
1. Acidosis (fall in pH)
2. Alkalosis (rise in pH)
3. Compensatory responses
4. Mixed Responses
Chemical Pathology of Acid-Base Disturbances
1. Metabolic Acidosis
2. Anion Gap
2-A. High Anion Gap Acidosis
2-B. Normal Anion Gap Acidosis
3. Metabolic Alkalosis
4. Respiratory Acidosis
5. Respiratory Alkalosis
8. Assessment of Acid–Base Parameters
Normal serum electrolyte values
Related Topics
CHAPTER 34:
Electrolyte and Water Balance
CHAPTER 35:
Body Fluids
MILK
CEREBROSPINAL FLUID (CSF)
AMNIOTIC FLUID
CHAPTER 36:
Mechanisms of Action of Hormones
CHAPTER 37:
Hypothalamic and Pituitary Hormones
1. HYPOTHALAMIC NEUROPEPTIDES
2. HYPOTHALAMIC RELEASING FACTORS
3. HORMONES OF ANTERIOR PITUITARY
CHAPTER 38:
Steroid Hormones
ADRENAL CORTICAL HORMONES
Assessment of Glucocorticoid Secretion
1. Basal level of cortisol
2. Estimation of urinary free cortisol
3. Plasma ACTH
4. Dexamethasone suppression test
5. Urinary steroids
6. Stimulation test
7. Metyrapone test
8. CRH test
Assessment of Adrenal Androgen Secretion
1. Adrenal Hyperfunction
2. Adrenal Hypofunction
Primary Hyperaldosteronism
(Conn's Syndrome)
Adrenogenital Syndrome (AG Syndrome)
11-Hydroxylase Deficiency
SEX HORMONES
CHAPTER 39:
Thyroid Hormones
SECTION F: MOLECULAR BIOLOGY
CHAPTER 40:
Nucleotides: Chemistry and Metabolism
BIOSYNTHESIS OF PURINE NUCLEOTIDES
Degradation of Purine Nucleotides
Species difference
Caffeine
URIC ACID
Disorders of Purine Metabolism
GOUT
Lesch-Nyhan Syndrome
Hypouricemia
Adenosine Deaminase Deficiency
DE NOVO SYNTHESIS OF PYRIMIDINE
Disorders of Pyrimidine Metabolism
Orotic Aciduria
Deoxy ribonucleotide Formation
Regulation of Deoxyribonucleotide Formation
Synthesis of Deoxythymine Nucleotides
Degradation of Pyrimidine Nucleotides
CHAPTER 41:
DNA–Deoxyribonucleic Acid: Structure and Replication
STRUCTURE OF DNA
Watson-Crick Model of DNA Structure
1. Right handed double helix
2. The base pairing rule
3. Hydrogen bonding
4. Antiparallel
5. Other features
Denaturation of DNA Strands
Higher Organisation of DNA
Histones
Nucleosomes
Further Condensation of DNA
Chromosomes
DNA is a Very Big Molecule
Activity of Chromatin
Inactivation of DNA During Differentiation
Introns, Exons, Cistrons
REPLICATION OF DNA
6. Details of DNA Replication
6-A. Initiation of DNA replication
6-B. Components of DNA replisome
7. RNA Primer is Required for DNA Synthesis
8. Elongation of DNA Strand
9. Discontinuous Synthesis
10. Lagging Strand and Okazaki Pieces
DNA REPAIR MECHANISMS
Diseases Associated with DNA Repair
1. Xeroderma Pigmentosum (XP)
2. Ataxia Telangectasia (AT)
Telomere and Telomerase
Hydrolysis of DNA
Inhibitors of DNA Replication
CHAPTER 42:
Transcription and Translation
RIBONUCLEIC ACID
1. TRANSCRIPTION PROCESS
2. Signals for Initiation of Transcription
2-A. Promoters
2-B. TATA Box in Prokaryotes
2-C. Golberg-Hogness Box in Eukaryotes
2-D. Enhancers and Silencers
3. Initiation of Transcription
3-A. Bacterial System
3-B. Mammalian System
4. Elongation Process of Transcription
5. Termination of Transcription
6. Post-transcriptional Processing
6-A. Poly-A Tailing at 3' End
6-B. Capping at 5' End
6-C. Methylations
7. Removal of Introns
7-A. Small Nuclear RNAs (snRNAs)
7-B. Spliceosomes
7-C. Ribozymes
Reverse Transcriptase
Inhibitors of RNA Synthesis
PROTEIN BIOSYNTHESIS
Transfer RNA (tRNA) or (sRNA)
A. Structure of tRNA Molecule
B. Acceptor Arm is at the 3' End
C. Anticodon Arm of tRNA
D. DHU Arm of tRNA
E. Pseudouridine Arm of tRNA
Ribosomal RNA (rRNA)
A. Components of rRNA
2-B. Bacterial Ribosomes are Different
Genetic Code
Salient Features of the Genetic Code
i. Triplet Codons
ii. Non-overlapping
iii. Non-punctuated
iv. Degenerate
v. Unambiguous
vi. Universal
vii. Wobbling Phenomenon
viii. Terminator Codons
ix. Initiator Codon
Mitochondria have different codes
TRANSLATION PROCESS
A. Activation of Amino Acid
B. Initiation of Protein Synthesis
B-1. Recognition steps
B-2. Formation of 80S ribosomal assembly
B-3. P and A Sites of Ribosomal Assembly
C. Elongation Process of Translation
C-1. Binding of New Amino Acyl tRNA
C-2. Peptide Bond Formation
C-3. Translocation Process
D. Energy Requirements
E. Termination Process of Translation
Polyribosomes
Protein Targetting
i. Proteins for external secretion
ii. Proteins for Internal Parts of the Cell
iii. Correct Address of Destination is Labelled
Post-translational Processing
A. Proteolytic cleavage
B. Modifications of amino acids
C. Subunit aggregation
D. Protein Folding
Inhibitors of Protein Synthesis
i. Reversible Inhibitors in Bacteria
ii. Irreversible Inhibitors in Bacteria
iii. Inhibitors of Protein Synthesis in Mammals
Mitochondrial DNA and RNA
New Concepts and Recent Developments
1. Genomics
2. Proteomics
3. Micro-RNA
4. Interfering RNA or RNAi
5. Antisense Therapy
6. Aptamers
CHAPTER 43:
Molecular Genetics and Control of Gene Expression
MUTATIONS
CELL CYCLE
REGULATION OF GENE EXPRESSION
Hormone Response Elements (HRE)
VIRUSES
CHAPTER 44:
Recombinant DNA Technology and Gene Therapy
RECOMBINANT DNA TECHNOLOGY
Applications of recombinant technology
1. Quantitative Preparation of Bio-molecules
2. Risk of Contamination is Eliminated
3. Specific Probes for Diagnosis of Diseases
4. Gene Therapy
Restriction Endonucleases (RE)
Restriction Sites
Restriction Map
VECTORS
Procedure of DNA recombination
1. Preparation of Specific Human Gene
2. Preparation of Chimeric DNA Molecules
3. Cloning of Chimeric DNA
4. Transfection of Vector into the Host
5. Plasmid Carries Antibiotic Resistance Genes
6. Selection of Colony having Desired Gene
7. Expression Vectors
Human Recombinant Proteins
Gene Library
Linkage Analysis
Human Genome Project (HGP)
GENE THERAPY
CHAPTER 45:
Molecular Biology Techniques
HYBRIDISATION AND BLOT TECHNIQUES
Applications of Molecular Cloning in Medicine
1. Diagnosis of Genetic Diseases
2. Detection of Specific Sequences
3. DNA Finger Printing in Forensic Medicine
Restriction Fragment Length Polymorphism (RFLP)
Clinical Applications of RFLP
POLYMERASE CHAIN REACTION (PCR)
Hybridoma Technology and Monoclonal Antibodies
1. Differences Between Monoclonal and Polyclonal Antibodies
2. Production of Hybridoma
3. Applications of monoclonal antibody
4. Advantages of monoclonal antibody
Transgenesis
Fusion Proteins
DNA Sequencing
Bioinformatics
Applications of Bioinformatics
CHAPTER 46:
Aids and Cancer
AIDS AND HIV
Natural Course of the Disease
1. Window Period
2. Seropositive Stage
3. AIDS Disease
4. Clinical Presentations
5. Laboratory Analysis
THE HUMAN IMMUNODEFICIENCY VIRUS
Immunology of AIDS
Genetic Resistance
Genetic Heterogeneity of Virus
ANTI-HIV DRUGS
Prevention
CANCER
ONCOGENIC VIRUSES
ONCOGENES
Anti-oncogenes or Onco-suppressor Genes
Growth Factors
TUMOUR KINETICS
Oncofetal Antigens
TUMOUR MARKERS
ANTICANCER DRUGS
SECTION G: CLINICAL BIOCHEMISTRY
CHAPTER 47:
Applications of Isotopes in Medicine
INTRODUCTION
ISOTOPES
RADIO-ACTIVITY
Radioactive Decay
1. Alpha Radiations
2. Beta Radiation
3. Gamma Radiation
Half-life of Radio-activity
Units of Radioactivity
1. Curie (Ci)
2. Rontgen (R)
3. Rad and Gray
4. Rem
Applications of Radioactivity in Research
Applications of Radioactivity for Diagnosis
Applications of Radioactivity in Treatment
a. Unsealed Sources
b. Sealed Sources
c. Teletherapy
Radiosensitivity
Fractionation of Doses
BIOLOGICAL EFFECTS OF RADIATION
Radiation Protection
Maximum permissible dose
CHAPTER 48:
Methods of Purification of Biological Compounds
ELECTROPHORESIS
CHROMATOGRAPHY
2. Partition Chromatography
2-A. Paper Chromatography
2-B. Thin Layer Chromatography (TLC)
2-C. Visualisation of Chromatography
2-D. Importance of Rf Value
3. Ion–Exchange Chromatography
4. Gel Filtration Chromatography
5. Affinity Chromatography
6. High Performance Liquid Chromatography
RADIO-IMMUNO-ASSAY (RIA)
ELISA Test
PRE-ANALYTICAL VARIATIONS
THE pH METER
COLORIMETER
SPECTROPHOTOMETER
FLAME PHOTOMETER
QUALITY CONTROL
CHAPTER 49:
Liver and Gastric Function Tests
GASTRIC FUNCTION
Assessment of Gastric Function
Pentagastrin Stimulation Test
Interpretations of Gastric Juice Analysis
Hyperacidity is seen in:
Hypoacidity is seen in:
Augmented Histamine Test
Estimation of Free Acidity and Total Acidity
Other Relevant Clinical Labortory Tests
CHAPTER 50:
Kidney function tests
RENAL FUNCTION TESTS
Reabsorption of Solutes in Tubules
1. Sodium
2. Calcium
3. Uric acid
4. Urea
5. Creatinine
6. Potassium
Reabsorption of Water
Clinical Applications
ABNORMAL CONSTITUENTS OF URINE
A. Physical Characteristics of Urine
B. Chemical Characteristics of Urine
1. Reaction to Litmus
2. Proteins
3. Blood
4. Reducing Sugars (Glycosuria)
5. Ketone Bodies
6. Bile Salts
7. Bile Pigments
8. Urobilinogen
Nonprotein Nitrogen (NPN)
MARKERS OF GFR
Clearance Tests
Definition
Creatinine Clearance Test
1. Importance of Creatinine Clearance
2. Normal Serum Creatinine Level
3. Procedure for Creatinine Clearance Test
4. Reference values for Creatinine Clearance
5. Interpretation of Creatinine Clearance
6. Creatinine co-efficient
Urea Clearance Test
1. Importance of Urea Clearance
2. Procedure
3. Maximum Urea Clearance
4. Standard Urea Clearance
5. Interpretation of Urea Clearance Value
Blood Urea Level
1. Normal Serum Urea Level
2. Interpretation of Blood Urea Value
3. Pre-renal Conditions
4. Renal Diseases
5. Post-renal Causes
6. Decreased Blood Urea
Inulin Clearance
Diodrast Clearance
MARKERS OF GLOMERULAR PERMEABILITY
TESTS FOR TUBULAR FUNCTION
Appendices
INDEX
TOC
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