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Textbook of Biochemistry for Medical Students
DM Vasudevan, Sreekumari S, Kannan Vaidyanathan
SECTION A: CHEMICAL BASIS OF LIFE
CHAPTER 1:
Biochemical Perspective to Medicine
BIOMOLECULES
STUDY OF METABOLIC PROCESSES
STABILIZING FORCES IN MOLECULES
Covalent Bonds
Ionic Bonds or Electrostatic Bonds
Hydrogen Bonds
Hydrophobic Interactions
Van der Waals Forces
WATER: THE UNIVERSAL SOLVENT
PRINCIPLES OF THERMODYNAMICS
First Law of Thermodynamics
Second Law of Thermodynamics
Gibbs Free Energy Concept
Standard Free Energy Change
Three Types of Reactions
DONNAN MEMBRANE EQUILIBRIUM
Clinical Applications of the Equation
LEARNING POINTS, CHAPTER 1
CHAPTER 2:
Subcellular Organelles and Cell Membranes
SUBCELLULAR ORGANELLES
Marker Enzymes
NUCLEUS
ENDOPLASMIC RETICULUM (ER)
GOLGI APPARATUS
LYSOSOMES
PEROXISOMES
MITOCHONDRIA
PLASMA MEMBRANE
Fluid Mosaic Model
Membrane Proteins
Bacterial Cell Wall
SPECIALIZED MEMBRANE STRUCTURES
Tight Junction
Microvilli
Membranes of Organelle
Cytoskeleton
TRANSPORT MECHANISMS
Passive Transport
Simple Diffusion
Facilitated Diffusion
Aquaporins
Ion Channels
Ligand-Gated Channels
Voltage-Gated Channels
Ionophores
Active Transport
Sodium Pump
Calcium Pump
Uniport, Symport and Antiport
Clinical Applications
Endocytosis
Pinocytosis
Receptor-Mediated Endocytosis
Secretory Vesicles and Exocytosis
Phagocytosis
Transcytosis
The ABC Family of Transporters
LEARNING POINTS, CHAPTER 2
CHAPTER 3:
Amino Acids: Structure and Properties
CLASSIFICATION OF AMINO ACIDS
Based on Structure
Special Groups in Amino Acids
Based on Side Chain
Based on Metabolism
Based on Nutritional Requirements
Naming (numbering) of Carbon Atoms
PROPERTIES OF AMINO ACIDS
Ampholyte and Isoelectric Point
Optical Activity
GENERAL REACTIONS OF AMINO ACIDS
Due to Carboxyl Group
Decarboxylation
Amide Formation
Due to Amino Group
Transamination
Oxidative Deamination
Formation of Carbamino Compound
Due to Side Chains
Transmethylation
Ester Formation by the OH Group
Reaction of the Amide Group
Reactions of SH Group
Amino Acid Derivatives of Importance
PEPTIDE BOND FORMATION
Color Reactions of Amino Acids and Proteins
LEARNING POINTS, CHAPTER 3
CHAPTER 4:
Proteins: Structure and Function
STRUCTURE OF PROTEINS (Organization of Proteins)
Primary Structure
Sequence of Amino Acids in Proteins
Characteristics of a Peptide Bond
Numbering of Amino Acids in Proteins
Branched and Circular Proteins
Primary Structure of Insulin
Proinsulin
Primary Structure Determines Biological Activity
Secondary Structure of Proteins
Alpha Helix
Beta-Pleated Sheet
Collagen Helix
Tertiary Structure
Quaternary Structure
Structure-function Relationship
Enzymes
Transport Proteins
Structural Proteins
STUDY OF PROTEIN STRUCTURE
Steps for Determining the Primary Structure
End Group Analysis
Sequencing
Partial Hydrolysis
Automatic Sequencing
Chemical Synthesis of Peptides
PHYSICAL PROPERTIES OF PROTEINS
PRECIPITATION REACTIONS OF PROTEINS
Salting Out
Isoelectric Precipitation
Precipitation by Organic Solvents
Precipitation by Heavy Metal Ions
Precipitation by Alkaloidal Reagents
CLASSIFICATION OF PROTEINS
Classification Based on Functions
Classification Based on Composition and Solubility
Simple Proteins
Conjugated Proteins
Derived Proteins
Classification Based on Shape
Globular Proteins
Fibrous Proteins
Classification Based on Nutritional Value
Nutritionally Rich Proteins
Incomplete Proteins
Poor Proteins
Biologically Important Peptides
QUANTITATIVE ESTIMATION
Kjeldahl's Procedure
Advantage
Disadvantage
Biuret Method
Advantage
Disadvantage
Lowry's Method
Advantage
Spectrophotometric Estimation
Advantage
Nephelometry
Turbidimetry
ELISA Test
Proteomics
LEARNING POINTS, CHAPTER 4
CHAPTER 5:
Enzymology: General Concepts and Enzyme Kinetics
CLASSIFICATION OF ENZYMES
IUBMB System of Classification
Class 1: Oxidoreductases
Class 2: Transferases
Class 3: Hydrolases
Class 4: Lyases
Class 5: Isomerases
Class 6: Ligases
COENZYMES
First Group of Coenzymes
Nicotinamide Adenine Dinucleotide (NAD+)
Second Group of Coenzymes
Adenosine Triphosphate (ATP)
Metalloenzymes
Cofactors
MODE OF ACTION OF ENZYMES
Lowering of Activation Energy
Acid Base Catalysis
Substrate Strain
Serine Proteases
Covalent Catalysis
Entropy Effect
Product Substrate Orientation Theory
MICHAELIS-MENTEN THEORY
FISCHER'S TEMPLATE THEORY
KOSHLAND'S INDUCED FIT THEORY
ACTIVE SITE OR ACTIVE CENTER OF ENZYME
THERMODYNAMIC CONSIDERATIONS
Exergonic or Exothermic Reaction
Isothermic Reaction
Endergonic or Endothermic Reaction
ENZYME KINETICS
FACTORS INFLUENCING ENZYME ACTIVITY
Enzyme Concentration
Effect of Substrate Concentration
Michaelis Constant
Double Reciprocal Plot
Cooperative Binding
Effect of Concentration of Products
Effect of Temperature
Effect of pH
Enzyme Activation
Enzyme Inhibition
Competitive Inhibition
Non-competitive Inhibition (Irreversible)
Uncompetitive Inhibition
Suicide Inhibition
Allosteric Regulation
Key Enzymes
Feedback Inhibition
Induction
Repression
Covalent Modification
Compartmentalization
SPECIFICITY OF ENZYMES
Absolute Specificity
Bond Specificity
Group Specificity
Stereospecificity
Ribozymes
Body Metabolism is Controlled by Enzymes
ISOENZYMES
Isoenzymes may be Formed in Different Ways
Identification of Isoenzymes
Related Topics
LEARNING POINTS, CHAPTER 5
CHAPTER 6:
Clinical Enzymology
CLINICAL ENZYMOLOGY
Cardiac Biomarkers
CREATINE KINASE (CK)
Reference Values
CK and Heart Attack
Isoenzymes of CK
CK and Muscle Diseases
CARDIAC TROPONINS (CTI/CTT)
Lactate Dehydrogenase (LDH) (LD)
Reference Values
LDH and Heart Attack
Differential Diagnosis
Isoenzymes of LDH
Brain Natriuretic Peptide (BNP)
Other Markers for Myocardial Infarction
Enzyme Profiles in Liver Diseases
Alanine AminoTransferase (ALT)
Aspartate aminotransferase (AST)
ALKALINE PHOSPHATASE (ALP)
Gamma-Glutamyltransferase (GGT)
Acid Phosphatase (ACP)
PROSTATE SPECIFIC ANTIGEN (PSA)
Cholinesterase (ChE)
Glucose-6-Phosphate Dehydrogenase (GPD)
AMYLASE
LIPASE
ENOLASE
Ceruloplasmin
Adenosine Deaminase
Enzymes in other Body Fluids and Cells
Enzymes as Therapeutic Agents
Enzymes Used in Diagnostic Techniques
Related Topics
Clinical Case Study 6.1
Clinical Case Study 6.2
Clinical Case Study 6.1 Answer
Clinical Case Study 6.2 Answer
LEARNING POINTS, CHAPTER 6
CHAPTER 7:
Chemistry of Carbohydrates
FUNCTIONS OF CARBOHYDRATES
NOMENCLATURE
STEREOISOMERS
Reference Carbon Atom of Sugars
D- and L-Isomerism of Glucose
Optical Activity
Diastereoisomers of Glucose
Epimerism of Aldoses
Anomerism of Sugars
Three Representations of Glucose Structure
Fructose is a Ketohexose
REACTIONS OF MONOSACCHARIDES
Enediol Formation
Benedict's Reaction
Osazone Formation
Oxidation of Sugars
Furfural Derivatives
Reduction to Form Alcohols
Glycosides
Formation of Esters
Amino Sugars
Deoxy Sugars
Pentoses
DISACCHARIDES
Sucrose
Lactose
Maltose
Isomaltose
POLYSACCHARIDES
Starch
Structure of Starch
Hydrolysis of Starch
Action of Amylases on Starch
Glycogen
Cellulose
Inulin
Dextrans
Chitin
HETEROGLYCANS
Agar
MUCOPOLYSACCHARIDES
Hyaluronic Acid
Heparin
Chondroitin Sulfate
Keratan Sulfate
Dermatan Sulfate
GlycoproteinS and Mucoproteins
Common Sugar Substitutes
Dietary Fiber
Bacterial Cell Wall
LEARNING POINTS, CHAPTER 7
CHAPTER 8:
Chemistry of Lipids
CLASSIFICATION OF LIPIDS
FATTY ACIDS
SATURATED FATTY ACIDS
UNSATURATED FATTY ACIDS
TRANS FATTY ACIDS (TFA)
Properties of Fatty Acids
Hydrogenation
Halogenation
Melting Point
Salt Formation
Ester Formation
Oxidation of Fatty Acids
NEUTRAL FATS
Nomenclature of Carbon Atoms
Mixed Triglycerides
Physical Properties of Triacylglycerols
Storage of Energy as Fat
Hydrolysis of Triacylglycerols (TAG)
Saponification
Iodine Number
Rancidity of Fat
Waxes
PHOSPHOLIPIDS
Phosphatidates
Amphipathic Nature
Micellar Formation
Liposomes
Aquasomes
Biomembranes
Phosphatidylcholine or Lecithin
Action of Phospholipases
Lung Surfactants
Phosphatidylethanolamine or Cephalin
Phosphatidylinositol
Plasmalogens
Phosphatidylglycerol
Sphingolipids
Phosphosphingosides
Sphingomyelins
Non-phosphorylated Lipids
Glycosphingolipids (Glycolipids)
Globosides (Ceramide Oligosaccharides)
Gangliosides
Sulfolipids or Sulfatides
Related Topics
LEARNING POINTS, CHAPTER 8
SECTION B: GENERAL METABOLISMGENERAL METABOLISM
CHAPTER 9:
Overview of Metabolism
EXPERIMENTAL STUDY OF METABOLISM
Level 1: Intact Organism
Level 2: Organ Perfusion
Level 3: Organ Slices
Level 4: Intact Cells and Tissue Culture Set-up
Level 5: Homogenates
Level 6A: Purified Enzymes
Level 6B: DNA or Genomics
Use of Radioisotope Tracers
Studies on Metabolism
METABOLISM
Types of Metabolic Pathways
Stages or Phases of Metabolism
METABOLIC PROFILE OF ORGANS
Brain
Skeletal Muscle
Adipose Tissue
Liver
Cardiac Muscle
Effect of Exercise on Metabolic Profile
Metabolic Adaptations during Starvation
First Stage: Glycogenolysis
Second Stage: Gluconeogenesis
Third Stage: Lipolysis
Fourth Stage: Acidosis
Fifth Stage: Death from Starvation
LEARNING POINTS, CHAPTER 9
CHAPTER 10:
Metabolic Pathways of Glucose
DIGESTION OF CARBOHYDRATES
Clinical Application; Lactose Intolerance
ABSORPTION OF CARBOHYDRATES
Absorption of Glucose
Co-transport from Lumen to Intestinal Cell
Another Uniport System Releases Glucose into Blood
Glucose Transporter 4
Absorption of other Monosaccharides
GLUCOSE METABOLISM
Clinical Importance of Glucose
GLYCOLYSIS (EMBDEN-MEYERHOF-PARNAS PATHWAY)
Significance of Glycolysis Pathway
Glucose Entry into Cells
Step 1 of Glycolysis
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 in Anaerobic Conditions
Energy Yield from Glycolysis in Aerobic Conditions
Regulation of Glycolysis
Factors Regulating Glycolysis
Cori Cycle or Lactic Acid Cycle
Pasteur Effect
Warburg Hypothesis
Rapoport Luebering Cycle (BPG Shunt)
Significance of BPG
METABOLIC FATE OF PYRUVATE
Pyruvate Dehydrogenase Complex
Importance of Pyruvate Dehydrogenase
Pyruvate as a Junction Point
GLUCONEOGENESIS
Definition
Site
Key Gluconeogenic Enzymes
Pyruvate Carboxylase Reaction
Malate Aspartate Shuttle
Phosphoenolpyruvate Carboxykinase
Partial Reversal of Glycolysis
Fructose-1,6-bisphosphatase
Glucose-6-phosphatase Reaction
Significance of Gluconeogenesis
Substrates for Gluconeogenesis
Lactate
Glucogenic Amino Acids
Glucose-Alanine Cycle (Cahill Cycle)
Glycerol
Propionyl-CoA
Regulation of Gluconeogenesis
Pyruvate Carboxylase
Fructose-1,6-bisphosphatase
ATP
Hormonal Regulation of Gluconeogenesis
GN Ratio or DN Ratio
GLYCOGEN METABOLISM
Functions of Glycogen
DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS
Glycogen Phosphorylase
Debranching by Bifunctional (Two) Enzymes
Phosphoglucomutase
Glucose-6-phosphatase in Liver
Muscle Lacks Glucose-6-phosphatase
Energetics
GLYCOGEN SYNTHESIS (GLYCOGENESIS)
Activation of Glucose
Glycogen Synthase
Branching Enzyme
Regulation of Glycogen Metabolism
Generation of Cyclic AMP (cAMP)
Protein Kinase Activation
Phosphorylase Kinase Activation
Glycogen Phosphorylase in Liver and Muscle
Glycogen Synthase
Summary of Regulation
GLYCOGEN STORAGE DISEASES
Glycogen Storage Disease Type-I
HEXOSE MONOPHOSPHATE (HMP) SHUNT PATHWAY
Overview of the Shunt Pathway
OXIDATIVE PHASE
Step 1 of HMP Pathway
Step 2 of HMP Pathway
Step 3, NADPH is again Generated
NON-OXIDATIVE PHASE
Step 4, Isomerization
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
Pathway is Significantly Active in the Following Organs
Generation of Reducing Equivalents
Free Radical Scavenging
Erythrocyte Membrane Integrity
Prevention of Methemoglobinemia
Detoxification of Drugs
Lens of Eye
Macrophage Bactericidal Activity
Availability of Ribose
What about ATP?
Clinical Significance of Shunt Pathway
GPD Deficiency
Methemoglobinemia
Thiamine Deficiency
GLUCURONIC ACID PATHWAY
Importance of the Glucuronic Acid Pathway
Effect of Drugs
Vitamin C in Lower Animals
Essential Pentosuria
Polyol Pathway of Glucose
Clinical Case Study 10.1
Clinical Case Study 10.2
Clinical Case Study 10.3
Clinical Case Study 10.4
Clinical Case Study 10.1 Answer
Clinical Case Study 10.2 Answer
Clinical Case Study 10.3 Answer
Clinical Case Study 10.4 Answer
LEARNING POINTS, CHAPTER 10
CHAPTER 11:
Regulation of Blood Glucose, Insulin and Diabetes Mellitus
REGULATION OF BLOOD GLUCOSE
Postprandial Regulation
Regulation in Fasting State
Determination of Glucose in Body Fluids
Enzymatic Method
Commonly Employed Terms Regarding Glucose
Conducting the Glucose Tolerance Test
Normal Values and Interpretations
Classical Oral Glucose Tolerance Test (OGTT)
Indications for OGTT
Preparation of the Patient
Causes for Abnormal GTT Curve
Impaired Glucose Tolerance (IGT)
Impaired Fasting Glycemia (IFG)
Gestational Diabetes Mellitus (GDM)
Alimentary Glucosuria
Renal Glucosuria
Factors Affecting GTT
REDUCING SUBSTANCES IN URINE
Lactosuria
Insulin
Structure of Insulin
Biosynthesis of Insulin
Secretion of Insulin
Factors Increasing Insulin Secretion
Degradation of Insulin
Mechanisms of Action of Insulin
Insulin Receptors
Signal Transduction
Gene Transcription (New Enzyme Synthesis)
Activation of Enzymes
Other Effects
Physiological Actions of Insulin (Metabolic Effects of Insulin)
Uptake of Glucose by Tissues
Utilization of Glucose
Hypoglycemic Effect
Lipogenesis
Anti-lipolytic Effect
Other General Effects
HYPERGLYCEMIC HORMONES
GLUCAGON
Physiological Actions of Glucagon
Mechanism of Action
Anti-insulin Hormones
DIABETES MELLITUS
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Diabetic Prone States
Secondary to Other Known Causes
Type 1 Diabetes Mellitus (T1DM)
Type 2 Diabetes Mellitus (T2DM)
Metabolic Syndrome (MetS)
Metabolic Syndrome (MetS) and Polycystic Ovary Syndrome (PCOS)
Pathological Alterations in Diabetes Mellitus
Derangements in Carbohydrate Metabolism
Derangements in Lipid Metabolism
Derangement in Protein Metabolism
Clinical Presentations in Diabetes Mellitus
Acute Complications OF DIABETES MELLITUS
Diabetic Ketoacidosis
Diagnosis of Ketosis
Lactic Acidosis
Chronic Complications of Diabetes Mellitus
Hyperosmolar Nonketotic Coma
Laboratory Investigations in Diabetes
Blood Glucose Level
Glycated Hemoglobin
Interpretation of Glycohemoglobin Values
Disadvantage of HbA1c estimation
How Frequently the Estimation to be Done
Fructosamines
Complete Lipid Profile
Kidney Function Tests
Microalbuminuria and Frank Albuminuria
Management of Diabetes Mellitus
Hypoglycemia
Clinical Case Study 11.1
Clinical Case Study 11.2
Clinical Case Study 11.3
Clinical Case Study 11.4
Clinical Case Study 11.5
Clinical Case Study 11.6
Clinical Case Study 11.7
Clinical Case Study 11.8
Clinical Case Study 11.9
Clinical Case Study 11.10
Clinical Case Study 11.1 Answer
Clinical Case Study 11.2 Answer
Clinical Case Study 11.3 Answer
Clinical Case Study 11.4 Answer
Clinical Case Study 11.5 Answer
Clinical Case Study 11.6 Answer
Clinical Case Study 11.7 Answer
Clinical Case Study 11.8 Answer
Clinical Case Study 11.9 Answer
Clinical Case Study 11.10 Answer
LEARNING POINTS, CHAPTER 11
CHAPTER 12:
Metabolic Pathways of Other Carbohydrates
FRUCTOSE METABOLISM
Hereditary Fructose Intolerance (HFI)
Fructosuria
GALACTOSE METABOLISM
Galactose Utilizing Steps
Galactosemia
Galactokinase Deficiency
METABOLISM OF ALCOHOL
Alcohol Dehydrogenase (ADH)
Aldehyde Dehydrogenase
Microsomal Ethanol Oxidizing System (MEOS)
Biochemical Alterations in Alcoholism
Chronic Alcoholism
Alcoholism and Liver
Alcoholism and Nervous System
Laboratory Findings in Chronic Alcoholism
METABOLISM OF AMINO SUGARS
GLYCOPROTEINS
Blood Group Substances (Antigens)
Proteoglycans
Biosynthesis of Glycoproteins
Congenital Disorders of Glycosylation (CDG)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Rheumatoid Arthritis
Viruses
Mucopolysaccharidoses
Clinical Case Study 12.1
Clinical Case Study 12.2
Clinical Case Study 12.3
Clinical Case Study 12.4
Clinical Case Study 12.1 Answer
Clinical Case Study 12.2 Answer
Clinical Case Study 12.3 Answer
Clinical Case Study 12.4 Answer
LEARNING POINTS, CHAPTER 12
CHAPTER 13:
Metabolism of Fatty Acids
DIGESTION OF LIPIDS
Digestion in Stomach
Digestion in Intestines
Bile Salts are Important for Digestion of Lipids
Lipolytic Enzymes in Intestines
Digestion of Triacylglycerols
Colipase
ABSORPTION OF LIPIDS
Absorption of Long Chain Fatty Acids
Mixed Micelle Formation
Enterohepatic Circulation of Bile Salts
Re-esterification Inside the Mucosal Cell
Chylomicrons
SCFA Absorption is Different
Abnormalities in Absorption of Lipids
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
Carnitine
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
Fate of Propionyl-CoA
Propionate is Gluconeogenic
Inborn Errors of Propionate Metabolism
ALPHA-OXIDATION
Refsum's Disease
Infantile Refsum's Disease
OMEGA OXIDATION
Inherited Disorders
DE NOVO SYNTHESIS OF Fatty acids
Transport of Acetyl-CoA to Cytoplasm
Fatty Acid Synthase (FAS) Complex
Advantages of Multi-enzyme Complex
First Domain or Condensing Unit
Second Domain or Reduction Unit
Third 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
Coenzymes of Fatty Acid Synthesis
Regulation of Fatty Acid Synthesis
Availability of Substrates
Acetyl-CoA Carboxylase
Insulin Favors Lipogenesis
Glucagon Inhibits Lipogenesis
Regulation at the Gene Level
SYNTHESIS OF TRIACYLGLYCEROLS
METABOLISM OF ADIPOSE TISSUE
Adipose Tissue in Well-fed Condition
Adipose Tissue in Fasting Condition
Adipose Tissue and Diabetes Mellitus
Adipose Tissue and Obesity
Adipokines
White Adipose Tissue
Liver-Adipose Tissue Axis
FATTY LIVER AND LIPOTROPIC FACTORS
Causes of Fatty Liver
Excessive Mobilization of Fat
Excess Calorie Intake
Toxic Injury to Liver
Alcoholism
Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)
Fatty Liver Progresses to Cirrhosis
Lipotropic Factors
METABOLISM OF KETONE BODIES
Ketogenesis
Step 1: Condensation
Step 2: Production of HMG-CoA
Step 3: Lysis
Step 4: Reduction
Step 5: Spontaneous Decarboxylation
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
Salient Features of Ketosis
Diagnosis of Ketosis
Differential Diagnosis of Ketosis
Management of Ketoacidosis
Clinical Case Study 13.1
Clinical Case Study 13.2
Clinical Case Study 13.3
Clinical Case Study 13.1 Answer
Clinical Case Study 13.2 Answer
Clinical Case Study 13.3 Answer
LEARNING POINTS, CHAPTER 13
CHAPTER 14:
Cholesterol and Lipoproteins
CHOLESTEROL
Clinical Significance of Cholesterol
Structure of Cholesterol
Absorption of Cholesterol
BIOSYNTHESIS OF CHOLESTEROL
Step 1: Condensation
Step 2: Production of HMG-CoA
Step 3: The Committed Step
Step 4: Production of 5 Carbon Unit
Step 5: Condensation of 5-Carbon Units
Step 6: Cyclization
Step 7: Cutting to Size
Regulation of Cholesterol Synthesis
Cholesterol Pool and Cholesterol Metabolism
Excretion of Cholesterol
Liver and Cholesterol
PLASMA LIPIDS
Classification of Lipoproteins
General Characteristics of Lipoproteins
Separation by Ultracentrifugation
Separation by Electrophoresis
Apo-lipoproteins
CHYLOMICRONS
Synthesis of Chylomicrons
Metabolism of Chylomicrons
Liver Takes up Chylomicron Remnants
Function of Chylomicrons
VERY LOW DENSITY LIPOPROTEINS
Synthesis of VLDL
Metabolism of VLDL
Function of VLDL
LOW DENSITY LIPOPROTEINS
Metabolism of LDL and LDL Receptors
Function of LDL
LDL and Clinical Applications
Lipoprotein (a)
HIGH DENSITY LIPOPROTEIN
Metabolism of HDL
Functions of HDL
Clinical Significance of HDL
HDL-specific Receptors
FREE FATTY ACID (FFA)
Functions of Cholesterol
FORMATION OF BILE ACIDS
Synthesis of Bile Acids
Hydroxylation Reactions
Removal of 3 Carbon Unit
Formation of Bile Salts
Secondary Bile Acids/Bile Salts
Functions of Bile Salts
Enterohepatic Circulation of Bile Salts
Bile
Functions of Bile
Cholesterol and Cardiac Diseases
LEARNING POINTS, CHAPTER 14
CHAPTER 15:
Hyperlipidemias and Cardiovascular Diseases
CLINICAL SIGNIFICANCE OF CHOLESTEROL
ATHEROSCLEROSIS
Atherosclerosis and LDL
Stage I: Formation of Foam Cells
Stage II: Progression of Atherosclerosis
Stage III: Fibrous proliferation
Stage IV: Advancing Fibrous Plaque
Myocardial Infarction (MI)
PLASMA LIPID PROFILE
RISK FACTORS FOR ATHEROSCLEROSIS
Serum Cholesterol Level
LDL-Cholesterol Level
HDL-Cholesterol Level
Apoprotein Levels and Ratios
Lp(a)
Non-HDL Cholesterol
High Sensitive C Reactive Protein (hsCRP)
Serum Triglyceride
Diabetes Mellitus
Smoking
Hypertension
Obesity and Sedentary Lifestyle
PREVENTION OF ATHEROSCLEROSIS
Reduce Dietary Cholesterol
Vegetable Oils and PUFA
Moderation in Fat Intake
Green Leafy Vegetables
Avoid Sucrose and Cigarette
Exercise
Hypolipidemic Drugs
Avoid Trans Fatty Acids (TFA)
PUFA, in Excess, may be Harmful
HYPOLIPOPROTEINEMIAS
Abetalipoproteinemia
Hypoalphalipoproteinemia
Tangier Disease
HYPERLIPIDEMIAS
Type IIA (Primary Familial Hypercholesterolemia)
Clinical Case Study 15.1
Clinical Case Study 15.2
Clinical Case Study 15.3
Clinical Case Study 15.1 Answer
Clinical Case Study 15.2 Answer
Clinical Case Study 15.3 Answer
LEARNING POINTS, CHAPTER 15
CHAPTER 16:
MCFA, PUFA, Prostaglandins and Compound Lipids
DIGESTION OF MEDIUM CHAIN FATTY ACIDS
Very Long Chain Fatty Acids (VLCFA)
MONOUNSATURATED FATTY ACIDS (MUFA)
Modified Beta-Oxidation of MUFA
Polyunsaturated Fatty Acids (pufa)
Lipid Peroxidation
Elongation of Fatty Acids
Desaturation of Fatty Acids
Essential Fatty Acids (EFA)
Gamma-Linolenic Acid (GLA)
Clinical Significance of Omega-3, and Omega-6 PUFAs
EICOSANOIDS
PROSTAGLANDINS
Chemical Structure
Classification of Prostaglandins
Biosynthesis of Prostaglandins
Regulation of Synthesis
Mechanism of Action
Biological Actions and Clinical Applications
Effects on CVS
Effects on Ovary and Uterus
Effects on Respiratory Tract
Effects on Immunity and Inflammation
Leukotrienes (LTs)
Lipoxins
SYNTHESIS OF COMPOUND LIPIDS
Synthesis of Glycerophosphatides
Synthesis of Phosphatidylinositol
Synthesis of Phosphatidyl Choline
Plasmalogens
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 (Sphingolipidoses)
Multiple Sclerosis
Clinical Case Study 16.1
Clinical Case Study 16.1 Answer
LEARNING POINTS, CHAPTER 16
CHAPTER 17:
General Amino Acid Metabolism (Urea Cycle and One-Carbon Metabolism)
DIGESTION OF PROTEINS
Gastric Digestion of Proteins
Rennin
Pepsin
Pancreatic Digestion of Proteins
Trypsin
Chymotrypsin
Carboxypeptidases
Intestinal Digestion of Proteins
Absorption of Amino Acids
Miester Cycle (Gamma-Glutamyl Cycle)
Food Allergy
Clinical Applications
Intracellular Protein Degradation
Cathepsins
Ubiquitin
Proteasomes
Interorgan Transport of Amino Acids
In Fasting State
In the Fed State
General Metabolism of Amino Acids
FORMATION OF AMMONIA
Transamination
Biological Significance of Transamination
First Step of Catabolism
Synthesis of Non-essential Amino Acids
Interconversion of Amino Acids
Exceptions
Clinical Significance of Transamination
Transdeamination
Oxidative Deamination of Glutamate
Minor Pathways of Deamination
Nonoxidative Deaminations
DISPOSAL/DETOXIFICATION OF AMMONIA
First Line of Defense (Trapping of Ammonia)
Transportation of Ammonia
Final Disposal
UREA CYCLE
Step 1: Formation of Carbamoyl Phosphate
Step 2: Formation of Citrulline
Step 3: Formation of Argininosuccinate
Step 4: Formation of Arginine
Step 5: Formation of Urea
Energetics of Urea Cycle
Regulation of the Urea Cycle
Coarse Regulation
Fine Regulation
Compartmentalization
Disorders of Urea Cycle
Hepatic Coma (Acquired Hyperammonemia)
Urea Level in Blood
Hyperammonemia
ONE-CARBON METABOLISM
Generation of One-Carbon Groups
Interconversion of One-Carbon Groups
Utilization of One-Carbon Groups
Clinical Case Study 17.1
Clinical Case Study 17.1 Answer
LEARNING POINTS, CHAPTER 17
CHAPTER 18:
Aliphatic Amino Acids
GLYCINE (GLY) (G)
Utilization of Glycine
Glycine Cleavage System
Glucogenic Pathway
Special Metabolic Functions of Glycine
CREATINE AND CREATINE PHOSPHATE
Synthesis of Heme
Synthesis of Purines
Synthesis of Glutathione
Glycine as a Conjugating Agent
Glycine as a Neurotransmitter
Glycine as a Constituent of Protein
Metabolic Errors in Relation to Glycine
Nonketotic Hyperglycinemia (NKH)
Primary Hyperoxaluria
SERINE (SER) (S)
Catabolism of Serine
Metabolic Functions of Serine
Choline Synthesis
Serine as a Component of Protein
Selenocysteine (SeCys) (21st amino acid)
ALANINE (ALA) (A)
Beta alanine
THREONINE (THR) (T)
METHIONINE (MET) (M)
Methionine in Transmethylation Reactions
CYSTEINE (CYS) (C)
Degradation of Cysteine
Metabolic Functions of Cysteine
Formation of Glutathione
Amino Acid Transport
Coenzyme Role
RBC Membrane Integrity
Met-Hemoglobin
Conjugation for Detoxification
Activation of Enzymes
Formation of Taurine
Metabolism of Sulfur
Formation of Active Sulfate
CYSTINURIA
Cyanide-Nitroprusside Test
Cystinosis
HOMOCYSTINURIAS
Cystathionine Beta Synthase Deficiency
Cystathioninuria
Acquired Hyperhomocysteinemias
ACIDIC AMINO ACIDS AND THEIR AMIDES
GLUTAMIC ACID (GLU) (E)
Gamma-Amino Butyric Acid (GABA)
GLUTAMINE (GLN) (Q)
Glutamate Transporters
ASPARTIC ACID (ASP) (D)
ASPARAGINE (ASN) (N)
Lysine (Lys) (K)
ARGININE (ARG) (R)
NITRIC OXIDE (NO˙)
Chemistry
Synthesis of Nitric Oxide
Metabolic Fate
Isoenzymes of NOS
Mechanism of Action of Nitric Oxide
Physiological Actions of Nitric Oxide
Nitric Oxide in Diseases and Treatment
POLYAMINES
Biochemical Functions of Polyamines
Biogenic Amines
BRANCHED CHAIN AMINO ACIDS (BCAA)
Maple Syrup Urine Disease (MSUD)
Isovaleric Aciduria
Clinical Case Study 18.1
Clinical Case Study 18.2
Clinical Case Study 18.3
Clinical Case Study 18.1 Answer
Clinical Case Study 16.2 Answer
Clinical Case Study 18.3 Answer
LEARNING POINTS, CHAPTER 18
CHAPTER 19:
Aromatic Amino Acids
PHENYLALANINE (PHE) (F)
Step 1: Phenylalanine to Tyrosine
TYROSINE (TYR) (T)
Catabolism of Tyrosine (and Phenylalanine)
Step 2: Transamination
Step 3: Production of Homogentisic acid
Step 4: Cleavage of Aromatic Ring
Step 5: Isomerization
Step 6: Hydrolysis
Important Specialized Products from Tyrosine
Synthesis of Melanin
Synthesis of Catecholamines
Actions of Epinephrine
Degradation of Adrenaline
Synthesis of Thyroid Hormones
Tyramine
PHENYLKETONURIA (PKU)
Biochemical Abnormalities
Clinical Manifestations
Laboratory Diagnosis
Treatment
ALKAPTONURIA
Biochemical Defect
Diagnosis of Alkaptonuria
ALBINISM
HYPERTYROSINEMIAS
Hepatorenal Tyrosinemia (Tyrosinemia Type I)
TRYPTOPHAN (TRP) (W)
Substances Produced from Tryptophan are
Major Catabolic Pathway of Tryptophan
Nicotinic Acid Pathway of Tryptophan
Serotonin
Functions of Serotonin
Catabolism of Serotonin
Carcinoid Tumors
Melatonin
Putrefaction of Tryptophan
Hartnup Disease
HISTIDINE (HIS) (H)
Histamine
Histidinemia
Urocanic Aciduria
PROLINE (PRO) (P) AND HYDROXYPROLINE
Fate of Carbon Skeletons of Amino Acids
AMINOACIDURIAS
Clinical Case Study 19.1
Clinical Case Study 19.1 Answer
LEARNING POINTS, CHAPTER 19
CHAPTER 20:
Citric Acid Cycle
REGULATION OF CITRIC ACID CYCLE
Citrate and Citrate Synthase
Availability and Cellular Need of ATP
Isocitrate Dehydrogenase
Alpha Ketoglutarate Dehydrogenase
Inhibitors of TCA Cycle
Metabolic Defects Related to Krebs Cycle
LEARNING POINTS, CHAPTER 20
CHAPTER 21:
Biological Oxidation and Electron Transport Chain
REDOX POTENTIALS
Negative and Positive Redox Potential
Substrate Level Phosphorylation
BIOLOGICAL OXIDATION
Electron Transport Chain
Energetics of Oxidative Phosphorylation
ENZYMES AND COENZYMES
Oxidases
Aerobic Dehydrogenases
Anaerobic Dehydrogenases
HIGH ENERGY COMPOUNDS
Adenosine Triphosphate (ATP)
Creatine Phosphate
Structure of Mitochondrion
ORGANIZATION OF ELECTRON TRANSPORT CHAIN
NADH Generation
Malate Aspartate Shuttle
ETC Complex I
Complex II
Coenzyme Q
Complex III or Cytochrome Reductase
Cytochrome c
Complex IV or Cytochrome Oxidase
Current Concept, Energetics of ATP Synthesis
Sites of ATP Synthesis
CHEMIOSMOTIC THEORY
Proton Pump and ATP Synthesis
ATP Synthase (Complex V)
Binding Change Mechanism
Regulation of ATP Synthesis
Inhibitors of ATP Synthesis
Site Specific Inhibitors (Table 21.4; Fig. 21.14)
How Does Shivering Produce Heat?
Brown Adipose Tissue and Heat Generation
Specific Inhibitors of ETC
Diseases Associated with Mitochondria
Mitochondrial Permeability Transition Pore (MPTP)
Mitochondrial Dysfunction and Insulin Resistance
Clinical Case Study 21.1
Clinical Case Study 21.2
Clinical Case Study 21.1 Answer
Clinical Case Study 21.2 Answer
LEARNING POINTS, CHAPTER 21
CHAPTER 22:
Heme Synthesis and Breakdown
STRUCTURE 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
DISORDERS OF HEME SYNTHESIS
Acute Intermittent Porphyria (AIP)
ALA Synthase (ALAS) Deficiency
Congenital Erythropoietic Porphyria
Porphyrias in General
Acquired Porphyrias
Diagnosis of Porphyrias
CATABOLISM OF HEME
Generation of Bilirubin
Transport to Liver
Conjugation in Liver
Excretion of Bilirubin to Bile
Fate of Conjugated Bilirubin in Intestine
Enterohepatic Circulation
Final Excretion
Plasma Bilirubin
Van den Bergh Test for Bilirubin
Tests for Bile Pigments
HYPERBILIRUBINEMIAS
Congenital Hyperbilirubinemias
Crigler-Najjar Syndrome
Gilbert's Disease
Dubin-Johnson Syndrome
Rotor Syndrome
Acquired Hyperbilirubinemias
Physiological Jaundice
Breast Milk Jaundice
Hemolytic Jaundice
Hemolytic Disease of the Newborn
Hemolytic Diseases of Adults
Hepatocellular Jaundice
Obstructive Jaundice
Bilirubin Toxicity
Clinical Case Study 22.1
Clinical Case Study 22.2
Clinical Case Study 22.3
Clinical Case Study 22.4
Clinical Case Study 22.5
Clinical Case Study 22.6
Clinical Case Study 22.1 Answer
Clinical Case Study 22.2 Answer
Clinical Case Study 22.3 Answer
Clinical Case Study 22.4 Answer
Clinical Case Study 22.5 Answer
Clinical Case Study 22.6 Answer
LEARNING POINTS, CHAPTER 22
CHAPTER 23:
Hemoglobin
STRUCTURE OF HEMOGLOBIN
Attachment of Heme with Globin Chain
TRANSPORT OF oxygeN BY HEMOGLOBIN
Oxygen Dissociation Curve (ODC)
Heme-Heme Interaction and Cooperativity
Effect of pH and pCO2
The Bohr Effect
The Chloride Shift
Effect of Temperature
Effect of 2,3-BPG
Adaptation to High Altitude
TRANSPORT OF CARBON DIOXIDE
Fetal Hemoglobin (HbF)
Hemoglobin A2
HEMOGLOBIN DERIVATIVES
Carboxy-Hemoglobin (Carbon Monoxy Hb) (CO-Hb)
Met-Hemoglobin (Met-Hb)
Met-Hemoglobinemias
Acquired or Toxic Met-Hemoglobinemia
Hemin Crystals
Glycated Hemoglobin
HEMOGLOBIN (globin chain) VARIANTS
Hemoglobinopathies
Sickle Syndromes
Unstable Hemoglobins
Hemoglobins with Abnormal Oxygen Affinity
Structural Variations Leading to Thalassemia
Nonsymptomatic Hemoglobin Variants
Hemoglobin S (HbS) (Sickle Cell Hemoglobin)
Sickle Cell Disease
Sickle Cell Trait
Electrophoresis
Sickling Test
Management of Sickle Cell Disease
Hemoglobin E
Hemoglobin C
Hemoglobin D
M-Hemoglobins (Hb M)
Inheritance of Hemoglobin Variants
THALASSEMIAS
Beta Thalassemia
Alpha Thalassemias
Thalassemia Syndromes
MYOGLOBIN
Clinical Significance of Myoglobin
ANEMIAS
Clinical Case Study 23.1
Clinical Case Study 23.2
Clinical Case Study 23.3
Clinical Case Study 23.1 Answer
Clinical Case Study 23.2 Answer
Clinical Case Study 23.3 Answer
LEARNING POINTS, CHAPTER 23
SECTION C: CLINICAL AND APPLIED BIOCHEMISTRY
CHAPTER 24:
Liver and Gastric Function Tests
PROBLEMS IN INTERPRETATION
FUNCTIONS OF LIVER
Synthetic Function
Carbohydrate Metabolism
Amino Acid Metabolism
Lipid Metabolism
Bilirubin Metabolism
Detoxification Functions
Excretory Functions
CLINICAL MANIFESTATIONS OF LIVER DYSFUNCTION
Jaundice
Portal Hypertension
Ascites
Markers of Hepatic Dysfunction
Measurement of Bilirubin(Test of Excretory Function of Liver)
Urinary Bilirubin
Urinary Urobilinogen
Urine Bile Salts
Causes of Jaundice
Tests Based on Synthetic Function of Liver
Serum Albumin Level
Serum Globulins
Prothrombin Time (PT)
Alpha-Fetoprotein (AFP)
Serum Electrophoresis
Tests Based on Serum Enzymes (Liver Enzyme Panel)
Enzymes Indicating Hepatocellular Damage
Markers of Obstructive Liver Disease
Alkaline Phosphatase (ALP)
Gamma-Glutamyltransferase (GGT)
Tests for Metabolic Capacity of Liver
Blood Ammonia
Immunological Tests in Liver Disease
Selection of Tests
Gastric Function Tests
Mechanism of HCl Secretion
Regulation of Acid Secretion
Assessment of Gastric Function
Pentagastrin Stimulation Test
Interpretations of Gastric Juice Analysis
Pancreatic Function Tests
Assessment of Pancreatic Function
STUDIES ON MALABSORPTION
Clinical Case Study 24.1
Clinical Case Study 24.2
Clinical Case Study 24.3
Clinical Case Study 24.1 Answer
Clinical Case Study 24.2 Answer
Gallstones
Clinical Case Study 24.3 Answer
Cholestasis of Pregnancy
LEARNING POINTS, CHAPTER 24
CHAPTER 25:
Kidney Function Tests
RENAL FUNCTION TESTS
Glomerular Function
Glomerular Filtration Rate (GFR)
Functions of the Tubules
Renal Threshold and Tubular Maximum
Reabsorption of Water
ABNORMAL CONSTITUENTS OF URINE
Physical Characteristics of Urine
Chemical Characteristics of Urine
Reaction to Litmus
Proteins
Blood
Reducing Sugars (Glycosuria)
Ketone Bodies
Bile Salts
Bile Pigments
Urobilinogen
Non-Protein Nitrogen (NPN)
MARKERS OF GLOMERULAR FILTRATION RATE
Clearance Tests
Definition
Creatinine Clearance Test
Importance of Creatinine Clearance
Reference Values of Creatinine
Interpretation of Creatinine Clearance
Estimated GFR (eGFR)
Creatinine Coefficient
Cystatin C as a Filtration Marker
Chronic Kidney Disease (CKD)
Acute Kidney Injury (AKI)
Urea Clearance Test
Importance of Urea Clearance
Maximum Urea Clearance
Standard Urea Clearance
Interpretation of Urea Clearance Value
Blood Urea Level
Interpretation of Blood Urea Value
Renal Diseases
Decreased Blood Urea
Azotemia
Inulin Clearance
Diodrast Clearance
MARKERS OF GLOMERULAR PERMEABILITY
Proteinuria
Glomerular Proteinuria
Microalbuminuria
Overflow Proteinuria
Tubular Proteinuria
Urogenic Proteinuria
TESTS FOR TUBULAR FUNCTION
Specific Gravity of Urine
Measurement of Osmolality
Concentration Test
Dilution Tests
Urinary Acidification
Clinical Case Study 25.1
Clinical Case Study 25.2
Clinical Case Study 25.3
Clinical Case Study 25.1 Answer
Clinical Case Study 25.2 Answer
Clinical Case Study 25.3 Answer
LEARNING POINTS, CHAPTER 25
CHAPTER 26:
Plasma Proteins
ELECTROPHORESIS
Normal Patterns and Interpretations
Abnormal Patterns in Clinical Diseases
ALBUMIN
Functions of Albumin
Colloid Osmotic Pressure of Plasma
Transport Function
Buffering Action
Nutritional Function
Clinical Applications
Blood Brain Barrier
Drug Interactions
Protein-Bound Calcium
Edema
Normal Value
Hypoalbuminemia
Albumin-Globulin Ratio
Hypoproteinemia
Hypergammaglobulinemias are Seen in
Low Albumin Level
Chronic Infections
Multiple Myeloma
TRANSPORT PROTEINS
ACUTE PHASE PROTEINS
C-Reactive Protein (CRP)
Ceruloplasmin
Wilson's Disease
Clinical Features
Alpha-1 Antitrypsin (AAT)
Alpha-2 Macroglobulin (AMG)
Negative Acute Phase Proteins
CLOTTING FACTORS
Prothrombin
Fibrinogen
Fibrinolysis
Clinical significance
ABNORMALITIES IN COAGULATION
Hemophilia A (Classical Hemophilia)
Clinical Case Study 26.1
Clinical Case Study 26.2
Clinical Case Study 26.1 Answer
Clinical Case Study 26.2 Answer
LEARNING POINTS, CHAPTER 26
CHAPTER 27:
Acid-Base Balance and pH
ACIDS AND BASES
Definition
Weak and Strong Acids
Dissociation Constant
Acidity of a Solution and pH
The Effect of Salt Upon the Dissociation
BUFFERS
Definition
Composition of a Buffer
Factors Affecting pH of a Buffer
Factors Affecting Buffer Capacity
How Do Buffers Act?
Application of the Equation
Effective Range of a Buffer
ACID-BASE BALANCE
Normal pH
Acidosis
Alkalosis
Volatile and Fixed Acids
Mechanisms of Regulation of pH
BUFFERS OF THE BODY FLUIDS
Bicarbonate Buffer System
Alkali Reserve
Phosphate Buffer System
Protein Buffer System
Relative Capacity of Buffer Systems
Buffers Act Quickly, but Not Permanently
RESPIRATORY REGULATION OF pH
The Second Line of Defense
Action of Hemoglobin
RENAL REGULATION OF PH
Excretion of H+; Generation of Bicarbonate
Reabsorption of Bicarbonate
Excretion of H+ as Titratable Acid
Excretion of Ammonium Ions
CELLULAR BUFFERS
Relationship of pH with K+ Ion Balance
DISTURBANCES IN ACID-BASE BALANCE
Classification of Acid-Base Disturbances
Acidosis (Fall in pH)
Alkalosis (Rise in pH)
Compensatory Responses
Mixed Responses
Biochemistry of Acid-Base Disturbances
Metabolic Acidosis
Anion Gap
High Anion Gap Metabolic Acidosis (HAGMA)
Normal Anion Gap Metabolic Acidosis (NAGMA)
Decreased Anion Gap is Seen in
Compensated Metabolic Acidosis
Clinical Features of Metabolic Acidosis
Treatment of Metabolic Acidosis
Metabolic Alkalosis
Clinical Features of Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis
Normal Serum Electrolyte Values
Related Topics
Clinical Case Study 27.1
Clinical Case Study 27.2
Clinical Case Study 27.3
Clinical Case Study 27.1 Answer
Clinical Case Study 27.2 Answer
Clinical Case Study 27.3 Answer
LEARNING POINTS, CHAPTER 27
CHAPTER 28:
Electrolyte and Water Balance
INTAKE AND OUTPUT OF WATER
OSMOLALITY OF ECF
Effective Osmolality
Regulation of Sodium and Water Balance
Antidiuretic Hormone (ADH)
Renin-Angiotensin System
Clinical Significance
Autoregulation
Disturbances in Fluid and Electrolyte Balance
Isotonic Contraction
Hypotonic Contraction
Hypertonic Contraction
Isotonic Expansion
Hypotonic Expansion
Hypertonic Expansion
SODIUM (NA+)
Edema
Hypernatremia
Hyponatremia
Treatment of Hyponatremia
POTASSIUM (K+)
Requirement
Sources
Normal Level
Potassium Excretion
Hypokalemia
Treatment of Hypokalemia
Hyperkalemia
Treatment of Hyperkalemia
CHLORIDE (CL-)
Hyperchloremia is seen in
Causes for Hypochloremia
Clinical Case Study 28.1
Clinical Case Study 28.2
Clinical Case Study 28.3
Clinical Case Study 28.4
Clinical Case Study 28.5
Clinical Case Study 28.1 Answer
Clinical Case Study 28.2 Answer
Clinical Case Study 28.3 Answer
Clinical Case Study 28.4 Answer
Clinical Case Study 28.5 Answer
LEARNING POINTS, CHAPTER 28
CHAPTER 29:
Body Fluids (Milk, CSF and Amniotic Fluid)
MILK
Lactose Synthesis
Lipids in Milk
Proteins in Milk
Minerals in Milk
Colostrum (Colostral Milk)
CEREBROSPINAL FLUID (CSF)
Biochemical Analysis of CSF
Glucose Level in CSF
AMNIOTIC FLUID
Lung Maturity
LEARNING POINTS, CHAPTER 29
CHAPTER 30:
Free Radicals and Antioxidants
CLINICAL SIGNIFICANCE
Chronic Inflammation
Acute Inflammation
Respiratory Diseases
Diseases of the Eye
Reperfusion Injury
Atherosclerosis and Myocardial Infarction
Ageing Process
Lipid Peroxidation
Initiation Phase
Propagation Phase
Termination Phase
Role of Antioxidants
Antioxidants
LEARNING POINTS, CHAPTER 30
CHAPTER 31:
Laboratory Techniques, Quality Control and Metabolic Diseases
ELECTROPHORESIS
Factors Affecting Electrophoresis
Electrophoresis Apparatus
Support Medium for Electrophoresis
Filter Paper
Agar or Agarose
Polyacrylamide Gel Electrophoresis (PAGE)
Visualization of Protein Bands
Immunoelectrophoresis
Ultracentrifugation
CHROMATOGRAPHY
Adsorption Chromatography
Partition Chromatography
Gel Filtration (Size Exclusion) Chromatography
High Pressure Liquid Chromatography (HPLC)
Ion Exchange Chromatography
Affinity Chromatography
RADIOIMMUNOASSAY (RIA)
ELISA TEST
Antibody Detection by ELISA
Antigen Detection by ELISA Method
COLORIMETER
Spectrophotometer
Ion-selective Electrodes
The pH Meter
AUTOANALYZER
Semiautomated Photometric Analyzers
Automatic Batch Analyzers
Discrete Selective Analyzers
Dry Chemistry Systems
MASS SPECTROMETRY
Tandem Mass Spectrometry (MS-MS)
REFERENCE VALUES
Reference Values and Observed Values
PREANALYTICAL VARIABLES
Noncontrollable Variables
SPECIMEN COLLECTION
Hemolysis
Anticoagulants
Storage and Preservation of Specimens
Care of Infected Specimens
Urine Collection
Timed Urine Specimen
Urine Preservatives
QUALITY CONTROL (QC)
Accuracy
Precision
Specificity
Sensitivity
Quality Control Charts
External Quality Assurances (EQAs)
PRENATAL DIAGNOSIS
Genetic Counseling
Amniocentesis
Chorionic Villi Sampling (CVS)
Cordocentesis
Cytogenetics and Molecular Cytogenetics
Biochemical Screening
Maternal Serum Screening
The Quadruple Test (Quad Screen)
Biochemical Genetics
Enzyme Assays and Molecular Techniques
NEWBORN SCREENING
Screening Technology
LABORATORY INVESTIGATIONS TO DIAGNOSE METABOLIC DISORDERS
Lactic Acidemia
Plasma and Urinary Amino Acids
Organic Acidurias
Lysosomal Storage Disorders (LSDs)
Mucopolysaccharide Screening
Urine Screening Tests
Other Clinical Biochemistry Topics
Clinical Case Study 31.1
Clinical Case Study 31.2
Clinical Case Study 31.3
Clinical Case Study 31.1 Answer
Clinical Case Study 31.2 Answer
Clinical Case Study 31.3 Answer
LEARNING POINTS, CHAPTER 31
SECTION D: NUTRITION
CHAPTER 32:
Fat Soluble Vitamins (A, D, E and K)
VITAMIN A
Chemistry
Absorption of Vitamin A
Transport from Liver to Tissues
Uptake by Tissues
Biochemical Role of Vitamin A
Wald's Visual Cycle
Dark Adaptation Mechanism
Rods are for Vision in Dim Light
Cones are for Color Vision
Colors have Profound Influence in Life
Other Biochemical Functions of Vitamin A
Deficiency Manifestations of Vitamin A
Night Blindness or Nyctalopia
Xerophthalmia
Bitot's Spots
Keratomalacia
Preventable Blindness
Skin and Mucous Membrane Lesions
Causes for Vitamin A Deficiency
Assessment of Deficiency
Daily Requirement of Vitamin A
Dietary Sources of Vitamin A
Therapeutic Use of Vitamin A
Hypervitaminosis A or Toxicity
VITAMIN D (CHOLECALCIFEROL)
Formation of Vitamin D
Activation of Vitamin D
Biochemical Effects of Vitamin D
Vitamin D and Absorption of Calcium
Effect of Vitamin D on Bone
Effect of Vitamin D on Renal Tubules
Regulation of Calcitriol Formation by Feedback Control
Deficiency of Vitamin D
Causes for Vitamin D Deficiency
Clinical Features of Rickets
Clinical Features of Osteomalacia
Different Types of Rickets
Other Actions of Vitamin D
Requirement of Vitamin D
Sources of Vitamin D
Hypervitaminosis D
VITAMIN E
Chemical Nature
Biochemical Role of Vitamin E
Inter-Relationship with Selenium
Deficiency Manifestations of Vitamin E
Recommended Daily Allowance
Sources of Vitamin E
Hypervitaminosis E
VITAMIN K
Chemistry of Vitamin K
Biochemical Role of Vitamin K
Vitamin K Dependent Carboxylase
Causes for Deficiency of Vitamin K
Clinical Manifestations of Deficiency
Daily Requirement of Vitamin K
Sources of Vitamin K
Hypervitaminosis K
Clinical Case Study 32.1
Clinical Case Study 32.1 Answer
LEARNING POINTS, CHAPTER 32
CHAPTER 33:
Water Soluble Vitamins
B COMPLEX GROUP OF VITAMINS
THIAMINE (VITAMIN B1)
Sources
Structure of Thiamine
Physiological Role of Thiamine
Deficiency Manifestations of Thiamine
Biochemical Parameters
Recommended Daily Allowance of Thiamine
RIBOFLAVIN (VITAMIN B2)
Structure of Riboflavin
Coenzyme Activity of Riboflavin
FAD Accepts Hydrogen
FMN-Dependent Enzymes
FAD-Dependent Enzymes
Riboflavin Deficiency
Dietary Sources of Riboflavin
Daily Requirement
NIACIN
Chemistry of Niacin
Coenzyme Forms of Niacin
One Hydrogen Atom and One Electron
NAD+ Dependent Enzymes
NADPH Dependent Reactions
Niacin Deficiency
Pellagra
Niacin is Synthesized from Tryptophan
Causes for Niacin Deficiency
Dietary Sources of Niacin
Recommended Daily Allowance (RDA)
Therapeutic Use of Niacin
Toxicity of Niacin
VITAMIN B6
Coenzyme Form
Functions of Pyridoxal Phosphate
Transamination
Decarboxylation
Sulfur Containing Amino Acids
Heme Synthesis
Production of Niacin
Glycogenolysis
Deficiency Manifestations of Pyridoxine
Neurological Manifestations
Dermatological Manifestations
Hematological Manifestations
Effect of Drugs on Vitamin B6
Dietary Sources of Vitamin B6
Requirement of B6
PANTOTHENIC ACID
Structure
Coenzyme Activity of Pantothenic Acid
Deficiency of Pantothenic Acid
Sources of Pantothenic Acid
Requirement of Pantothenic Acid
BIOTIN
Structure of Biotin
Coenzyme Activity of Biotin
Biotin Requiring CO2 Fixation Reactions
Acetyl-CoA carboxylase
Propionyl-CoA Carboxylase
Pyruvate Carboxylase
Biotin-Independent Carboxylation Reactions
Biotin Antagonists
Deficiency of Biotin
Requirement of Biotin
Sources of Biotin
FOLIC ACID
Chemistry of Folic Acid
Absorption of Folic Acid
Coenzyme Functions of Folic Acid
Causes for Folate Deficiency
Deficiency Manifestations
Reduced DNA synthesis
Macrocytic Anemia
Hyperhomocysteinemia
Birth Defects
Assessment of Folate Deficiency
Sources of Folic Acid
Recommended Daily Allowance (RDA)
Folic Acid Therapy
Folate Antagonists
Sulfonamides
Pyrimethamine
Aminopterin and Amethopterin
VITAMIN B12
Chemistry
Cyanocobalamin
Hydroxycobalamin
Adenosylcobalamin (Ado-B12)
Methylcobalamin
Absorption of Vitamin B12
Transport and Storage
Functional Role of B12
Methylmalonyl-CoA Isomerase
Homocysteine Methyl Transferase
Methyl Folate Trap and Folate Deficiency
Causes of B12 Deficiency
Nutritional
Decrease in Absorption
Addisonian Pernicious Anemia
Gastric Atrophy
Pregnancy
Fish Tapeworm
Deficiency Manifestations
Assessment of B12 Deficiency
Treatment
Requirement of Vitamin B12
Dietary Sources
CHOLINE
Biochemical Functions
INOSITOL
Biochemical Functions of Inositol
ASCORBIC ACID (VITAMIN C)
Chemistry of Vitamin C
Biosynthesis of Ascorbic Acid in Animals
Metabolism of Ascorbic Acid
Biochemical Functions of Vitamin C
Reversible Oxidation-Reduction
Hydroxylation of Proline and Lysine
Tryptophan Metabolism
Tyrosine Metabolism
Iron Metabolism
Hemoglobin Metabolism
Folic Acid Metabolism
Steroid Synthesis
Antioxidant Property
Cataract
Deficiency Manifestations of Vitamin C
Scurvy
Infantile Scurvy (Barlow's Disease)
Hemorrhagic Tendency
Internal Hemorrhage
Oral Cavity
Bones
Anemia
Dietary Sources of Vitamin C
Requirement of Vitamin C
Therapeutic Use of Vitamin C
Clinical Case Study 33.1
Clinical Case Study 33.2
Clinical Case Study 33.3
Clinical Case Study 33.4
Clinical Case Study 33.5
Clinical Case Study 33.6
Clinical Case Study 33.1 Answer
Clinical Case Study 33.2 Answer
Clinical Case Study 33.3 Answer
Clinical Case Study 33.4 Answer
Clinical Case Study 33.5 Answer
Clinical Case Study 33.6 Answer
LEARNING POINTS, CHAPTER 33
CHAPTER 34:
Mineral Metabolism and Abnormalities
CALCIUM (CA)
Sources of Calcium
Daily Requirement of Calcium
Absorption
Mechanism of Absorption of Calcium
Factors Causing Increased Absorption
Factors Causing Decreased Absorption
Calcium in Cells
Functions of Calcium
Activation of Enzymes
Muscles
Nerve Conduction
Secretion of Hormones
Second Messenger
Vascular Permeability
Coagulation
Myocardium
Bone and Teeth
Calcium in Blood
Factors Regulating Blood Calcium Level
Vitamin D
Parathyroid Hormone (PTH)
Mechanism of Action of PTH
Calcitonin
Calcitonin, Calcitriol and PTH Act Together
Procalcitonin (PCT)
Phosphorus
Children
Serum Proteins
Alkalosis and Acidosis
Hypercalcemia
Hypocalcemia
Tetany
Bone Mineralization and Demineralization
Osteoporosis
PHOSPHORUS
Requirement and Source
Serum Level of Phosphorus
MAGNESIUM (MG)
Requirement
Normal Serum Level of Magnesium
Functions of Magnesium
Hypomagnesemia
Hypermagnesemia
SULFUR (S)
Functions of Sulfur
Excretion
IRON (FE)
Distribution of iron
Requirement of Iron (ICMR)
Sources of Iron
Factors Influencing Absorption of Iron
Reduced Form of iron
Ascorbic Acid
Interfering Substances
Other Minerals
Mucosal Block Theory
Iron Transport in Blood and Uptake by Cells
Storage of Iron
Iron is Conserved
Excretion of Iron
Iron Deficiency Anemia
Microscopic Appearance
Clinical Manifestations
Laboratory Findings
Treatment of Iron Deficiency
Iron Toxicity
COPPER (CU)
Functions of Copper
Abnormal Metabolism of Copper
Copper Toxicity
IODINE (I)
ZINC (ZN)
Zinc Deficiency Manifestations
Acrodermatitis Enteropathica
Requirement of Zinc
Zinc Toxicity
FLUORIDE
Fluorosis is more Dangerous than Caries
SELENIUM (SE)
MANGANESE (MN)
LITHIUM (Li)
Related Topics
Clinical Case Study 34.1
Clinical Case Study 34.2
Clinical Case Study 34.3
Clinical Case Study 34.4
Clinical Case Study 34.5
Clinical Case Study 34.1 Answer
Clinical Case Study 34.2 Answer
Clinical Case Study 34.3 Answer
Clinical Case Study 34.4 Answer
Clinical Case Study 34.5 Answer
LEARNING POINTS, CHAPTER 34
CHAPTER 35:
Energy Metabolism and Nutrition
CALORIFIC VALUE
Respiratory Quotient
Energy Requirements of a Normal Person
Basal Metabolic Rate
Definition
Measurement of BMR
Factors Affecting BMR
Normal Value for BMR
Specific Dynamic Action (SDA)
Physical Activity
Requirements of Dietary Nutrients
Proximate Principles
IMPORTANCE OF CARBOHYDRATES
Dietary Carbohydrates
Sucrose
Dietary Fiber
NUTRITIONAL IMPORTANCE OF LIPIDS
Neutral Fats or Triacylglycerols
Cholesterol and Heart Diseases
Recommended Daily Intake of Fat
IMPORTANCE OF PROTEINS
Essential Amino Acids
Nitrogen Balance
Factors Affecting Nitrogen Balance
Maintenance of Nitrogen Balance
Nutritional Values (Nutritional Indices)
Assessment of Nutritional Values
Biological Value (BV) of Protein
Net Protein Utilization (NPU)
Limiting Amino Acids
Mutual Supplementation
PROTEIN ENERGY MALNUTRITION
Biochemical Alterations in PEM
Treatment of Protein-Energy Malnutrition
Sequelae of Protein Calorie Malnutrition
OBESITY
Diseases Related to Obesity
Treatment of Obesity
Regulators of Appetite
Adipose Tissue Talks to Brain through Factors
PRESCRIPTION OF DIET
General Principles
First Step: Calorie Requirement
Second Step: Proximate Principles
Third Step: General Composition of Food
Fourth Step: Food items
Fifth Step: Prescribing a Normal Diet
Diet for Patients with Diabetes
Glycemic Index
Clinical Case Study 35.1
Clinical Case Study 35.2
Clinical Case Study 35.3
Clinical Case Study 35.1 Answer
Clinical Case Study 35.2 Answer
Clinical Case Study 35.3 Answer
LEARNING POINTS, CHAPTER 35
CHAPTER 36:
Detoxification and Biotransformation of Xenobiotics
CYTOCHROME P450
Phases of Detoxification Processes
PHASE ONE REACTIONS
Oxidative Reactions
Reduction Reactions
Hydrolysis
PHASE TWO REACTIONS; CONJUGATIONS
Glucuronic Acid
Sulfate Conjugation
Cysteine and Glutathione
Acetylation
Conjugation with Glycine
Conjugation with Glutamine
Methylation Reactions
PHASE THREE REACTIONS
Related Topics
Clinical Case Study 36.1
Clinical Case Study 36.1 Answer
LEARNING POINTS, CHAPTER 36
CHAPTER 37:
Environmental Pollution and Heavy Metal Poisons
CORROSIVES
Cyanide Poisoning
IRRITANTS
Phosphorus
Neurotoxins
HEAVY METAL POISONS
Lead Poisoning
Sources of Lead Poison
Signs and Symptoms of Lead Poisoning
Treatment of Lead Poisoning
Mercury Poisoning
Elemental Mercury
Organic Mercury
Aluminium Toxicity
Arsenic Toxicity
PESTICIDES AND INSECTICIDES
Dichlorodiphenyltrichloroethane
Organophosphorus Compounds
OCCUPATIONAL AND INDUSTRIAL HAZARDS
Methanol
AIR POLLUTANTS
Industrial Pollution
Passive Cigarette Smoking
Other Obnoxious Indoor Agents
Toxic Substances in Foodstuffs
Toxins Normally Present in Plants
Storage Contamination
Adulterants
Toxins Entering during Food Preparation
Related Topics
Clinical Case Study 37.1
Clinical Case Study 37.1 Answer
LEARNING POINTS, CHAPTER 37
SECTION E: MOLECULAR BIOLOGY
CHAPTER 38:
Nucleotides: Chemistry and Metabolism
COMPOSITION OF NUCLEOTIDES
Bases Present in the Nucleic Acids
Purine Bases
Minor Purine Bases
Pyrimidine Bases
Nucleosides
Nucleotides
Nucleoside Triphosphates
Digestion of Nucleic Acids
BIOSYNTHESIS OF PURINE NUCLEOTIDES
Step 0 (Preparatory Step), PRPP Synthesis
Formation of AMP
Conversion of IMP to GMP
Salvage Pathway
Regulation of Purine Synthesis
Structural Analogs as Purine Synthesis Inhibitors
Purine Nucleoside Di- and Triphosphates
Degradation of Purine Nucleotides
Caffeine
URIC ACID
Disorders of Purine Metabolism
GOUT
Primary Gout
Abnormal 5-phosphoribosyl Amidotransferase
Abnormal PRPP Synthetase
Deficiency of Enzymes of Salvage Pathway
Glucose-6-phosphatase Deficiency
Secondary Hyperuricemia
Increased Production of Uric Acid
Reduced Excretion Rate
Clinical Findings of Gout
Treatment Policies in Gout
Lesch-Nyhan Syndrome
Hypouricemia
Adenosine Deaminase (ADA) Deficiency
DE NOVO SYNTHESIS OF PYRIMIDINE
Regulation of Pyrimidine Synthesis
DISORDERS OF PYRIMIDINE METABOLISM OROTIC ACIDURIA
Deoxyribonucleotide Formation
Synthesis of Deoxythymine Nucleotides
Anticancer Agents Acting on Pyrimidines
Degradation of Pyrimidine Nucleotides
Clinical Case Study 38.1
Clinical Case Study 38.2
Clinical Case Study 38.3
Clinical Case Study 38.1 Answer
Clinical Case Study 38.2 Answer
Clinical Case Study 38.3 Answer
LEARNING POINTS, CHAPTER 38
CHAPTER 39:
Deoxyribonucleic Acid: Structure and Replication
STRUCTURE OF DNA
Polarity of DNA Molecule
Watson-Crick Model of DNA Structure
Right Handed Double Helix
Base Pairing Rule
Hydrogen Bonding
Antiparallel
Other Features
Denaturation of DNA Strands
Higher Organization of DNA
Histones
DNA is a Very Long Molecule
Inactivation of DNA during Differentiation
Introns, Exons, Cistron
Repeat Sequences of DNA
REPLICATION OF DNA
Meselson-Stahl Experiment (1958)
Origin of Replication
Components of DNA Replisome
DNA Polymerase
Bacterial DNA Polymerases
Mammalian DNA Polymerases
RNA Primer is Required for DNA Synthesis
Elongation of DNA Strand
Discontinuous Synthesis and Okazaki Pieces
Modification after Replication
DNA REPAIR MECHANISMS
Exonucleolytic Proofreading
Mismatch Repair
Nucleotide Excision Repair (NER)
Base Excision Repair (BER)
Mutations
Diseases Associated with DNA Repair
Xeroderma Pigmentosum
Ataxia Telangiectasia
Telomere and Telomerase
Hydrolysis of DNA
Inhibitors of DNA Replication
LEARNING POINTS, CHAPTER 39
CHAPTER 40:
Transcription
RIBONUCLEIC ACID
Central Dogma of Molecular Biology
Replication, Transcription and Translation
Template and Coding Strands
Messenger RNA or mRNA
TRANSCRIPTION PROCESS
Mammalian RNA Polymerases
Signals for Initiation of Transcription
Promoters
TATA Box and Golberg-Hogness Box
Other Regulatory Signals
Initiation of Transcription
Bacterial System
Mammalian System
Elongation Process of Transcription
Termination of Transcription
Post-transcriptional Processing
Removal of Introns
Small Nuclear RNAs (snRNAs)
Spliceosomes
Processing of rRNA
Processing of tRNA
Ribozymes
Reverse Transcriptase
Inhibitors of RNA Synthesis
Interfering RNA or RNAi or siRNA
Antisense Therapy
LEARNING POINTS, CHAPTER 40
CHAPTER 41:
Genetic Code and Translation
PROTEIN BIOSYNTHESIS
Transfer RNA (tRNA)
Structure of tRNA Molecule
Acceptor Arm is at the 3’ End
Anticodon Arm of tRNA
DHU Arm of tRNA
Pseudouridine Arm of tRNA
Processing of tRNA
Ribosomal RNA (rRNA)
Components of rRNA
Bacterial Ribosomes are Different
Genetic Code
Salient Features of the Genetic Code
Triplet Codons
Nonoverlapping
Nonpunctuated
Degenerate
Unambiguous
Universal
Wobbling Phenomenon
Terminator Codons
Initiator Codon
Mitochondria have Different Codons
TRANSLATION PROCESS
Activation of Amino Acid (Charging Reaction)
Initiation of Protein Synthesis
Recognition Steps
Formation of Preinitiation Complex
Binding of mRNA
Formation of 80S Ribosomal Assembly
Elongation Process of Translation
Binding of New Amino Acyl tRNA
Peptide Bond Formation
Translocation Process
Energy Requirements
Termination Process of Translation
Polyribosomes
Protein Targeting
Proteins for External Secretion
Correct Address of Destination is Labeled
Post-translational Processing
Proteolytic Cleavage
Modifications of Amino Acids
Subunit Aggregation
Inhibitors of Protein Synthesis
Reversible Inhibitors in Bacteria
Irreversible Inhibitors in Bacteria
Inhibitors of Protein Synthesis in Mammals
Mitochondrial DNA and RNA
Genomics and Proteomics
LEARNING POINTS, CHAPTER 41
CHAPTER 42:
Control of Gene Expression
BASIC PRINCIPLES OF HEREDITY
Dominant Inheritance
Autosomal Recessive Inheritance
Sex-linked (X-linked) Recessive Inheritance
Marriages with Close-Cousins are Inadvisable
Genetic Disorders
Treatment Policies of Genetic Diseases
MUTATIONS
CLASSIFICATION OF MUTATIONS
Substitution
Deletion
Insertion
Effects of Mutations
Silent Mutation
Missense but Acceptable Mutation
Missense; Partially Acceptable Mutation
Missense; Unacceptable Mutation
Nonsense; Terminator Codon Mutation
Frameshift Mutation
Conditional Mutations
Mutagens and Mutagenesis
Lethal Mutations
Silent Mutations
Beneficial Mutations
Carcinogenic Effect
Site-directed Mutagenesis
CELL CYCLE
Cell Cycle Controls or Checkpoints
Retinoblastoma (RB) Oncosuppressor Protein
The p53 Oncosuppressor Protein
Apoptosis (Programmed Cell Death)
REGULATION OF GENE EXPRESSION
Induction and Repression
Operon Concept of Gene Regulation
The Lac Operon
Transcription is Normally Repressed
Derepression of Lac Operon
Clinical Applications
Regulation of Genes by Repression
Hormone Response Elements (HRE)
VIRUSES
Epigenetic Regulation
Clinical Case Study 42.1
Clinical Case Study 42.1 Answer
LEARNING POINTS, CHAPTER 42
CHAPTER 43:
Recombinant DNA Technology and Gene Therapy
RECOMBINANT DNA TECHNOLOGY
Applications of Recombinant Technology
Quantitative Preparation of Biomolecules
Risk of Contamination is Eliminated
Specific Probes for Diagnosis of Diseases
Gene Therapy
Restriction Endonucleases (RE)
Restriction Sites
VECTORS
Procedure of DNA Recombination
Preparation of Specific Human Gene
Preparation of Chimeric DNA Molecules
Cloning of Chimeric DNA
Transfection of Vector into the Host
Expression Vectors
Human Recombinant Proteins
Human Genome Project (HGP)
GENE THERAPY
What is Gene Therapy?
Summary of the Procedure
How the Genes are Introduced?
The Vectors
Retroviruses
Accomplishments
Obstacles to Success
STEM CELLS
LEARNING POINTS, CHAPTER 43
CHAPTER 44:
Molecular Diagnostics and Genetic Techniques
HYBRIDIZATION AND BLOT TECHNIQUES
Probes
Southern Blot Technique
Northern Blotting for Identifying RNA
Western Blot Analysis for Proteins
In Situ Hybridization
Microarray Technique
Animal Cloning
Applications of Cloning ofAnimals and Plants
Disadvantages of Cloning
Applications of Molecular Cloning in Medicine
Diagnosis of Genetic Diseases
DNA Finger Printing in Forensic Medicine
Restriction Fragment Length Polymorphism
Clinical Applications of RFLP
POLYMERASE CHAIN REACTION
Clinical Applications of PCR
Reverse Transcriptase PCR (RT-PCR)
Real-time PCR
Multiplex-PCR
Hybridoma Technology and Monoclonal Antibodies
Differences between Monoclonal and Polyclonal Antibodies
Production of Hybridoma
Applications of Monoclonal Antibody
Advantages of Monoclonal Antibody
Single Nucleotide Polymorphism (SNP)
Transgenesis
DNA Sequencing
Clinical Case Study 44.1
Clinical Case Study 44.1 Answer
LEARNING POINTS, CHAPTER 44
SECTION F: ADVANCED BIOCHEMISTRY
CHAPTER 45:
Hormones and Growth Factors
HORMONES ACTING THROUGH CYCLIC AMP
Signal Transduction through G-Protein
G-Protein Activates Adenyl Cyclase
Subunit Activation of G-Protein
Inactivation
Cyclic AMP
Second Messenger Activates PKA
Kinase Phosphorylates the Enzymes
There are Many G-proteins
There are Many Protein Kinases
CALCIUM-BASED SIGNAL TRANSDUCTION
HORMONES ACTING THROUGH PIP2 CASCADE
Role of Cyclic GMP
Hormones with Intracellular Receptors
Insulin-Signaling Pathway
HYPOTHALAMIC AND PITUITARY HORMONES
HYPOTHALAMIC NEUROPEPTIDES
ANTIDIURETIC HORMONE
Oxytocin
Hypothalamic-Releasing Factors
HORMONES OF ANTERIOR PITUITARY
GROWTH HORMONE
ADRENOCORTICOTROPIC HORMONE
Endorphins
Glycoprotein Hormones
THYROID-STIMULATING HORMONE (THYROTROPIN)
GONADOTROPINS
Human Chorionic Gonadotropin
Prolactin (Somatomammotropin)
Human Placental Lactogen
ADRENAL CORTICAL HORMONES
SYNTHESIS OF STEROID HORMONES
Secretion of Adrenal Hormones
Transport and Metabolism
Urinary Steroids
Biological Effects of Glucocorticoids
Biological Effects of Mineralocorticoids
MECHANISM OF ACTION OF STEROID HORMONES
Assessment of Glucocorticoid Secretion
Basal Level of Cortisol
Estimation of Urinary Free Cortisol
Plasma ACTH
Dexamethasone Suppression Test
Urinary Steroids
Stimulation Test
Metyrapone Test
CRH Test
Adrenal Hyperfunction
Adrenal Hypofunction
Primary Hyperaldosteronism (Conn's Syndrome)
Aldosterone in Blood
Adrenogenital Syndrome (AG Syndrome)
SEX HORMONES
OVARIAN HORMONES
Regulation of Ovarian Hormones
TESTICULAR HORMONES
THYROID HORMONES
Iodine Metabolism
Synthesis and Secretion of Thyroxine
Step 1: Uptake of Iodine
Step 2: Oxidation of Iodine
Step 3: Iodination
Step 4: Coupling
Step 5: Storage
Step 6: Utilization
Step 7: Hydrolysis
Step 8: Release
Step 9: Salvaging of Iodine
Step 10: Transport of Thyroid Hormones
Step 11: Catabolism of Thyroid Hormones
Mechanism of Action of Thyroid Hormone
METABOLIC EFFECTS OF THYROID HORMONES
Thyroid Function Tests
Assay of Hormones
Free T3 (fT3) and fT4
Plasma TSH
TRH Response Test
Cholesterol
Detection of Thyroid Antibodies
Abnormalities of Thyroid Function
HYPERTHYROIDISM
HYPOTHYROIDISM
Euthyroid Goiter
Congenital Hypothyroidism
GUT HORMONES
Hormones Regulating Digestion of Food
Peptide Hormones Regulating Food Intake
Adipose Tissue Derived Hormones
ADIPONECTIN
Cholecystokinin (CCK)
Glucose-Dependent Insulinotropic Polypeptide
Gastrin
Glucagon-like Peptides
Ghrelin
Neuropeptide Y
Secretin
Somatostatin
Vasoactive Intestinal Polypeptide
GROWTH FACTORS
EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)
Erythropoietin (EPO)
HER2/NEU
PLATELET DERIVED GROWTH FACTOR (PDGF)
Vascular Endothelial Growth Factor (VEGF)
Related topics
Clinical Case Study 45.1
Clinical Case Study 45.2
Clinical Case Study 45.3
Clinical Case Study 45.4
Clinical Case Study 45.5
Clinical Case Study 45.1 Answer
Clinical Case Study 45.2 Answer
Clinical Case Study 45.3 Answer
Clinical Case Study 45.4 Answer
Clinical Case Study 45.5 Answer
LEARNING POINTS, CHAPTER 45
CHAPTER 46:
Immunochemistry
STRUCTURE OF IMMUNOGLOBULINS
Heavy and Light Chains
Variable and Constant Regions
Different Classes of Immunoglobulins
lmmunoglobulin G (IgG)
Immunoglobulin M (IgM)
Immunoglobulin A (IgA)
Immunoglobulin E (IgE)
PARAPROTEINEMIAS
Multiple Myeloma (Plasmacytoma)
Bence-Jones Proteinuria
Hypergammaglobulinemia
Hypogammaglobulinemia
Primary and Secondary Immune Responses
Molecular Structure of Antigens
HLA Antigens
Soluble Factors
Interleukins (IL)
Clinical Case Study 46.1
Clinical Case Study 46.2
Clinical Case Study 46.1 Answer
Clinical Case Study 46.2 Answer
LEARNING POINTS, CHAPTER 46
CHAPTER 47:
Biochemistry of AIDS and HIV
EPIDEMIC OF AIDS
Indian Scenario
Transmission
Natural Course of the Disease
Window Period
Seropositive Stage
AIDS Disease
Clinical Presentations
Laboratory Diagnosis of AIDS
HUMAN IMMUNODEFICIENCY VIRUS
Structure
Virus Entry
Replication of HIV
HIV Genes
Immunology of AIDS
Genetic Heterogeneity of Virus
ANTI-HIV DRUGS
Prevention
Clinical Case Study 47.1
Clinical Case Study 47.1 Answer
LEARNING POINTS, CHAPTER 47
CHAPTER 48:
Biochemistry of Cancer
ETIOLOGY OF CANCER
Mutagens
Aflatoxins
Cigarette
Progression
Action of Chemical Carcinogens
Physical Carcinogens
Antimutagens
ONCOGENIC VIRUSES
ONCOGENES
Oncogenes are Normal Constituents of Cells
Proto-oncogenes are Regulatory Genes
Many Factors Activate Oncogenes
Antioncogenes or Oncosuppressor Genes
Growth Factors
Malignant Transformation
Tumor Immunology
Oncofetal Antigens
TUMOR MARKERS
Clinically Important Tumor Markers
Alpha-Fetoprotein (AFP)
Carcinoembryonic Antigen (CEA)
Beta Chain of Chorionic Gonadotropin
Carbohydrate Antigen 125 (CA-125)
Prostate Specific Antigen (PSA)
Estrogen Receptor (ER)
Progesterone Receptor (PR)
HER2/neu (or erbB-2, or EGFR2)
ANTICANCER DRUGS
Methotrexate
6-Mercaptopurine
Monoclonal Antibody
Related Topics
Clinical Case Study 48.1
Clinical Case Study 48.1 Answer
LEARNING POINTS, CHAPTER 48
CHAPTER 49:
Tissue Proteins in Health and Disease
COLLAGEN
Structure of Collagen
Synthesis of Collagen
Post-translational Modifications
Glycosylation of Procollagen
Triple Stranded Helix
Quarter Staggered Arrangement
Crosslinks in Collagen Fibers
Functions of Collagen
Degradation of Collagen
Abnormalities in Collagen
Osteogenesis Imperfecta
Ehlers-Danlos Syndrome (EDS)
Marfan's Syndrome
Menke's Disease
Deficiency of Ascorbic Acid
Hyperhomocysteinemia
Lathyrism
ELASTIN
Keratins
MUSCLE PROTEINS
Myosin
Actin
Troponins
Transduction of Chemical Energy to Mechanical Energy
Inherited Diseases due to Abnormality of Proteins
LENS PROTEINS
Crystallins
Cataracts
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
Familial AD and Apo-E4 gene
Protein Misfolding Diseases
LEARNING POINTS, CHAPTER 49
CHAPTER 50:
Applications of Isotopes in Medicine
INTRODUCTION
Isotopes
Atomic Number and Atomic Weight
RADIOACTIVITY
Radioactive Decay
Alpha Decay
Beta Radiation
Gamma Radiation
Half-life of Radioactivity
UNITS OF RADIOACTIVITY
Curie (Ci)
Becqueral (Bq)
Roentgen (R)
Rad and Gray
Applications of Radioactivity in Research
Applications of Radioactivity for Diagnosis
Applications of Radioactivity in Treatment
Unsealed Sources
Sealed Sources
Teletherapy
Radiosensitivity
BIOLOGICAL EFFECTS OF RADIATION
Direct Effects on Cancer Tissues
Effects of Radiation on Normal Tissues
Effects on Skin
Effects on Mucous Membrane
Effects on Blood Cells
Effects on Reproductive Organs
Carcinogenic Potential
Radiation Protection
Maximum Permissible Dose
LEARNING POINTS, CHAPTER 50
APPENDICES
APPENDIX I:
Abbreviations Used in this Book
APPENDIX II:
Reference Values
APPENDIX III:
Conversion Chart
APPENDIX IV:
Greek Alphabet
APPENDIX V:
Recommended Daily Allowance (RDA) of Essential Nutrients
APPENDIX VI:
Composition of Nutrients in Selected Common Food Materials
INDEX
TOC
Index
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