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Textbook of Biochemistry for Dental Students
DM Vasudevan, Sreekumari S
1:
Subcellular Organelles and Cell Membranes
INTRODUCTION
BIOMOLECULES
SUBCELLULAR ORGANELLES
1. Nucleus
2. Endoplasmic Reticulum (ER)
3. Golgi Apparatus
4. Lysosomes
5. Mitochondria
6. Plasma Membrane
7. Cytoskeleton
TRANSPORT MECHANISMS
1. Simple Diffusion
2. Facilitated Diffusion
3. Ion Channels
3-a) Ligand gated channels
3-b) Amelogenin
3-c) Voltage Gated Channels
4. Active Transport
5. Uniport, Symport and Antiport
2:
Amino Acids and Proteins
CLASSIFICATION OF AMINO ACIDS
PROPERTIES OF AMINO ACIDS
3-A. Decarboxylation
3-B. Amide Formation
4. Reactions due to Amino Group
4-A. Transamination
4-B. Oxidative Deamination
5. Reactions due to Side Chains
5-A. Ester Formation by OH Group
5-B. Reaction of the Amide Group
5-C. Reactions of SH Group
6. Special Functions of Amino Acids
7. Colour Reactions of Amino Acids and Proteins
8. Peptide Bond Formation
STRUCTURE OF PROTEINS (ORGANISATION OF PROTEINS)
1-A. Numbering of Amino Acids in Proteins
1-B. Branched Proteins
1-C. Pseudopeptides
1-D. Primary Structure of Insulin
1-E. Pro-insulin
1-F. Primary structure determines activity
2. Secondary Structure of Proteins
2-A. Different types of non-covalent bonds
2-B. Alpha helix
2-C. Beta-pleated sheet
3. Tertiary Structure
4. Quaternary Structure
5. Structure–Function Relationship
5-A. Hemoglobin
5-B. Collagen
6. End Group Analysis
PHYSICAL PROPERTIES OF PROTEINS
5-A. Salting Out
5-B. Iso-electric Precipitation
5-C. Precipitation by Organic Solvents
5-D. Precipitation by Heavy Metal Ions
5-E. Anionic or Alkaloidal Reagents
6. Denaturation of Proteins
7. Heat Coagulation
CLASSIFICATION OF PROTEINS
2-A. Simple Proteins
2-B. Conjugated Proteins
2-C. Derived Proteins
3. Classification based on Nutritional Value
3-A. Nutritionally rich proteins
3-B. Incomplete proteins
3-C. Poor proteins
QUANTITATIVE ESTIMATION OF PROTEINS
1. Kjeldahl's Procedure
2. Biuret Method
3. Lowry's Method
Related Topics
3:
Enzymology
CLASSIFICATION OF ENZYMES
IUBMB system of nomenclature of enzymes
Class 1 is called Oxidoreductases
CO-ENZYMES
Nicotinamide Adenine Dinucleotide (NAD+)
Second Group of Co-enzymes
Adenosine Triphosphate (ATP)
Salient features of Co-enzymes
Metallo-enzymes
MODE OF ACTION OF ENZYMES
1. Lowering of Activation Energy
2. Michaelis-Menten Theory
3. Fischer's Template Theory
4. Koshland's Induced Fit Theory
ACTIVE SITE OR ACTIVE CENTRE
THERMODYNAMICS
1. Exergonic or exothermic reaction
2. Isothermic reaction
3. Endergonic or endothermic reaction
ENZYME KINETICS
Salient features of Equilibrium
FACTORS INFLUENCING ENZYME ACTIVITY
1. Enzyme Concentration
2. Substrate Concentration
2-A. Michaelis Constant
2-B. Definition of Km
3. Effect of Concentration of Products
4. Effect of Temperature
5. Effect of pH
ENZYME ACTIVATION
ENZYME INHIBITION
1. Competitive Inhibition
1-A. Clinical Significance
2. Non-competitive Inhibition
3. Allosteric Regulation
Key Enzymes
Induction
Repression
ISO-ENZYMES
CLINICAL ENZYMOLOGY
Enzyme Units
Lactate Dehydrogenase (LDH)
LDH and Heart Attack
Iso-enzymes of LDH
Creatine Kinase (CK)
CK and Muscle Diseases
Iso-enzymes of CK
ALANINE AMINO TRANSFERASE (ALT)
4:
Carbohydrates-I: Chemistry, Digestion and Absorption of Carbohydrates
NOMENCLATURE
STEREOISOMERS
Optical Activity
Diastereo-isomers of Glucose
Glucose, Mannose and Galactose
Epimerism of Aldoses
Anomerism of Sugars
Three Representations of Glucose Structure
Fructose is a Ketohexose
REACTIONS OF MONOSACCHARIDES
1. Enediol Formation
2. Benedict's Reaction
3. Osazone Formation
4. Reduction to Form Alcohols
5. Oxidation of Sugars
6. Furfural Derivatives
7. Action of Alkali (Caramelisation)
8. Glycosides
9. Formation of Esters
10. Amino Sugars
11. Deoxy Sugars
12. Pentoses
DISACCHARIDES
1. Sucrose
2. Lactose
3. Maltose
4. Isomaltose
POLYSACCHARIDES
1. Starch
2. Glycogen
3. Cellulose
4. Inulin
5. Chitin
HETEROGLYCANS
1. Agar
2. Mucopolysaccharides
3. Hyaluronic Acid
4. Heparin
5. Chondroitin Sulphate
6. Keratan Sulphate
GLYCOPROTEINS AND MUCOPROTEINS
DIGESTION OF CARBOHYDRATES
Lactose Intolerance
ABSORPTION OF CARBOHYDRATES
1. Co-transport from Lumen to Intestinal Cell
2. Release of Glucose into Blood
3. GluT2 in Other Tissues
4. GluT4 in Muscle and Adipose Tissue
5:
Carbohydrates-II: Metabolic Pathways of Glucose
GLUCOSE METABOLISM
Importance of Glucose are:
GLYCOLYSIS
CORI's CYCLE OR LACTIC ACID CYCLE
1. Hormones
2. Phospho Fructo Kinase (PFK)
3. Hexokinase and Glucokinase
4. Pyruvate Kinase
Rapaport leubering cycle (BPG Shunt)
METABOLIC FATE OF PYRUVATE
Pyruvate Dehydrogenase Complex
Pyruvate as a Junction Point
GLUCONEOGENESIS
1. Pyruvate Carboxylase Reaction
2. Malate Shuttle
3. Phosphoenol Pyruvate Carboxy Kinase
4. Reversal of Glycolysis
5. Fructose-1,6-bisphosphatase
6. Glucose-6-phosphatase
Energy Requirement for Gluconeogenesis
Substrates for Gluconeogenesis
1. Lactate
2. Glucogenic Amino Acids
3. Glycerol
4. Propionyl CoA
Regulation of Gluconeogenesis
1. Hormonal Regulation of Gluconeogenesis
2. Physiological Significance
GLYCOGEN METABOLISM
1. Glycogen Phosphorylase
2. Debranching Needs Two Enzymes
3. Phospho gluco mutase
4. Glucose-6-phosphatase in Liver
5. Muscle lacks glucose-6-phosphatase
Glycogen Synthesis (Glycogenesis)
1. Activation of Glucose
2. Glycogen Synthase
3. Brancher Enzyme
Regulation of Glycogen Metabolism
1. Generation of Cyclic AMP (cAMP)
2. Summary of Regulation
Functions of Glycogen
GLYCOGEN STORAGE DISEASES
Glycogen Storage Disease Type-I
HEXOSE MONOPHOSPHATE (hmp) PATHWAY
Overview of the Shunt Pathway
A. Oxidative Phase
Step 1 of HMP pathway
Step 2 of HMP pathway
Step 3, NADPH is again generated
Non-Oxidative Phase
Regulation of HMP Shunt Pathway
Significance of the HMP Shunt Pathway
1. Tissues
2. Generation of reducing equivalents
3. Erythrocyte membrane
4. Lens of eye
5. Availability of Ribose
6. What about ATP?
7. GPD deficiency
8. Met-hemoglobinemia
6:
Carbohydrates-III: Regulation of Blood Sugar and Diabetes Mellitus
REGULATION OF BLOOD GLUCOSE
Factors Maintaining Blood Sugar
Post-prandial Regulation
Regulation in Fasting State
NORMAL PLASMA GLUCOSE LEVEL
Sugar in Urine
Effects of Hormones on Glucose Level in Blood
ORAL GLUCOSE TOLERANCE TEST (OGTT)
Indications for OGTT
Contraindications for OGTT
Preparation of the Patient
Conducting the Glucose Tolerance Test
Normal Values and interpretations
Diagnostic Criteria for Diabetes Mellitus
Causes for Abnormal GTT Curve
1. Impaired Glucose Tolerance (IGT)
2. Gestational Diabetes Mellitus (GDM)
3. Alimentary Glucosuria
4. Renal Glucosuria
Factors Affecting GTT
Corticosteroid Stressed GTT
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
Structure of insulin
Biosynthesis of insulin
Factors increasing insulin secretion
Physiological Actions of Insulin or Mechanisms of Action of Insulin or Metabolic Effects of Insulin
1. Insulin Receptors
2. Uptake of Glucose by Tissues
3. Utilisation of Glucose
4. Hypoglycemic Effect
5. Lipogenesis
6. Anti-lipolytic Effect
7. Anti-ketogenic Effect
HYPERGLYCEMIC HORMONES
GLUCAGON
Physiological Actions of Glucagon
Other Anti-insulin Hormones
DIABETES MILLITUS
1. Type 1 Diabetes Mellitus
2. Type 2 Diabetes Mellitus
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 sugar estimations
2. Glyco-hemoglobin estimation
Management of Diabetes Mellitus
7:
Carbohydrates-IV: Metabolic Pathways of Other Sugars
GLUCURONIC ACID PATHWAY OF GLUCOSE
Importance of the glucuronic acid pathway
Vitamin C in lower animals
Essential Pentosuria
FRUCTOSE METABOLISM
Hereditary Fructose Intolerance (HFI)
Fructosuria
GALACTOSE METABOLISM
Galactose Catabolism
Galactosemia
METABOLISM OF ALCOHOL
1. Alcohol Dehydrogenase (ADH)
2. Aldehyde Dehydrogenase
3. Biochemical Alterations in Alcoholism
Mucopolysaccharidoses
8:
Saliva and Dental Caries
COMPOSITION OF TEETH
Trace Elements
Organic Components
DENTAL CARIES
Microbiological Organisms Cause Dental Caries
Sucrose is Needed in the Diet to Cause Caries
Streptococcus mutans
Pathology of Caries
Prevention of Caries
FLUORIDE
Fluoride is Useful to Prevent Caries
Fluorosis is More Dangerous than Caries
Incidence of Fluorosis
Prevention of Fluorosis
9:
Lipids-I: Chemistry
CLASSIFICATION OF LIPIDS
I. Simple Lipids
II. Compound Lipids
A) Phospholipids, Containing Phosphoric Acid
B) Non-phosphorylated Lipids
III. Derived Lipids
IV. Lipids Complexed to Other Compounds
FATTY ACIDS
CLASSIFICATION OF FATTY ACIDS
1. Depending on Total No. of Carbon Atoms
2. Depending on Length of Hydrocarbon Chain
3. Depending on Nature of Hydrocarbon Chain
SATURATED FATTY ACIDS
UNSATURATED FATTY ACIDS
Clinical Significance of PUFA
Properties of Fatty Acids
NEUTRAL FATS
1. Nomenclature of Carbon Atoms
2. Mixed Triglycerides
3. Physical Properties of Triglycerides
4. Storage of Energy as Fat
5. Hydrolysis of Triglycerides
6. Saponification
7. Iodine Number
8. Rancidity of Fat
Waxes
PHOSPHOLIPIDS
A. Phosphatidates
B. Amphipathic Nature
C. Biomembranes
D. Liposomes
1. Phosphatidyl choline or Lecithin
2. Phosphatidyl ethanolamine or Cephalin
3. Plasmalogens
4. Sphingolipids
Phosphosphingosides
NON-PHOSPHORYLATED LIPIDS
LIPID STORAGE DISEASES OR SPHINGOLIPIDOSES
Niemann-Pick Disease
Gaucher's Disease
Tay-Sachs Disease
Essential Fatty Acids
Eicosanoids
PROSTAGLANDINS (PGs)
Biosynthesis of Prostaglandins
Regulation of Synthesis
Biological Actions
10:
Lipids-II: 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 Triglycerides
Co-lipase
ABSORPTION OF LIPIDS
1. Mixed Micelle Formation
2. Enterohepatic Circulation of Bile Salts
3. Re-esterification Inside the Mucosal Cell
4. Chylomicrons
5. SCFA Absorption is Different
6. Abnormalities in Absorption of Lipids
7. Fate of Chylomicrons
BETA-OXIDATION OF FATTY ACIDS
Preparative Step 1: Activation of Fatty Acids
Preparative Step 2: Role of Carnitine
Preparative Step-3: Carnitine Acyl Transferase
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
OXIDATION OF ODD-CHAIN FATTY ACIDS
Fate of Propionyl CoA
Propionate is Gluconeogenic
Inborn Errors of Propionate Metabolism
DE NOVO SYNTHESIS OF FATTY ACIDS
Transport of Acetyl CoA to Cytoplasm
Fatty Acid Synthase (FAS) Complex
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
Regulation of Fatty Acid Synthesis
SYNTHESIS OF TRIGLYCERIDES (TAG)
Liver-adipose Tissue Axis
FATTY LIVER AND LIPOTROPIC FACTORS
Causes of Fatty Liver
1. Excessive mobilization of fat
2. Excess calorie intake
3. Toxic injury to liver
4. Alcoholism
5. Fatty liver progresses to cirrhosis
Lipotropic Factors
METABOLISM OF KETONE BODIES
Step 1. Condensation
Step 2. Production of HMG CoA
Step 3. Lysis
Step 4. Reduction
Step 5. Spontaneous decarboxylation
KETOSIS
A. Causes for Ketosis
B. Regulation of Ketogenesis
Level 1: Lipolysis
Level 2: Entry of Fatty Acid to Mitochondria
Level 3: Oxidation of Acetyl CoA
C. Consequences of Ketosis
D. Diagnosis of Ketosis
E. Differential Diagnosis
F. Management of Ketoacidosis
11:
Lipids-III: Cholesterol, Lipoproteins and Cardiovascular Diseases
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 Inside Cells
Excretion of Cholesterol
PLASMA LIPIDS
General Characteristics of Lipoproteins
Apolipoproteins
1. CHYLOMICRONS
Synthesis of Chymomicrons
Meta bolism of Chylomicrons
Liver Takes Chylomicron Remnants
Function of Chylomicrons
2. VERY LOW DENSITY LIPOPROTEINS
Synthesis of VLDL
Metabolism of VLDL
Function of VLDL
3. LOW DENSITY LIPOPROTEINS (LDL)
Metabolism of LDL and LDL Receptors
Function of LDL
LDL and Clinical Applications
Lipoprotein (a)
4. HIGH DENSITY LIPOPROTEIN (HDL)
Metabolism of HDL
Function of HDL
Clinical significance of HDL
5. FREE FATTY ACID (FFA)
HYPERLIPIDEMIAS
Type IIA (Primary Familial Hypercholesterolemia)
ATHEROSCLEROSIS
Atherosclerosis and LDL
SERUM CHOLESTEROL IS INCREASED IN
RISK FACTORS FOR ATHEROSCLEROSIS
1. Serum cholesterol level
2. LDL-cholesterol level
3. HDL-cholesterol level
4. Apoprotein levels and ratios
5. Lp(a)
6. Cigarette smoke
7. Hypertension
8. Diabetes mellitus
9. Serum triglyceride
10. Obesity and sedentary life style
PREVENTION OF ATHEROSCLEROSIS
1. Reduce dietary cholesterol
2. Vegetable oils and PUFA
3. Moderation in fat intake
4. Green leafy vegetables
5. Avoid sucrose and cigarette
6. Exercise
7. Hypolipidemic drugs
12:
Amino Acid Metabolism
DIGESTION OF PROTEINS
1. Rennin
2. Pepsin
B. Pancreatic Digestion of Proteins
3. Trypsin
4. Chymotrypsin
5. Carboxypeptidases
C. Intestinal Digestion of Proteins
6. Aminopeptidases
ABSORPTION OF AMINO ACIDS
CLINICAL APPLICATIONS
GENERAL METABOLISM OF AMINO ACIDS
FORMATION OF AMMONIA
Biological Significance of Transamination
1. First step of catabolism
2. Synthesis of non-essential amino acids
3. Interconversion of amino acids
Clinical Significance of Transamination
B. Transdeamination
Oxidative Deamination of Glutamate
DISPOSAL/DETOXIFICATION OF AMMONIA
1. First Line of Defense (Trapping of Ammonia)
2. Transportation of Ammonia
3. 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
1. Coarse Regulation
2. Fine Regulation
3. Compartmentalization
Disorders of Urea Cycle
Urea Level in Blood
Formation of Glycin
Utilization of Glycine
1. Glycine Cleavage System
2. Glucogenic Pathway
3. Special Metabolic Functions of Glycine
4. Creatine and Creatine Phosphate
A. First step (Guanido acetic acid)
B. Second step (Creatine)
C. Third step (Creatine phosphate)
D. Fourth step (Creatinine)
E. Clinical applications
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
A. Activation of methionine to SAM
B. Conversion of methionine to cysteine
Methionine in Transmethylation Reactions
Formation of Cysteine
DEGRADATION OF CYSTEINE
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
Cystinuria
Homocystinuria
Cystathioninuria
Step 1: Phenylalanine to tyrosine
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
1. Synthesis of Melanin
Clinical Applications of Melanin
2. Synthesis of Catecholamines
2-A. Tyrosine Hydroxylase
2-B. DOPA-decarboxylase
2-C. Norepinephrine
2-D. Epinephrine
Actions of Epinephrine
2-E. Degradation of Adrenaline
3. Synthesis of Thyroid Hormones
PHENYLKETONURIA (PKU)
Biochemical Abnormalities in PKU
Clinical Manifestations
Laboratory Diagnosis
Treatment
ALKAPTONURIA
Biochemical Defect
Diagnosis of Alkaptonuria
ALBINISM
Nicotinic Acid Pathway of Tryptophan
Serotonin
Functions of Serotonin
Catabolism of Serotonin
Carcinoid Tumors
Melatonin
Putrefaction of Tryptophan
Histamine
Summary of Metabolism of Amino Acids
Fate of Carbon skeletons
13:
Plasma Proteins
ELECTROPHORESIS
Normal Values and Interpretations
Abnormal Patterns in Clinical Diseases
ALBUMIN
TRANSPORT PROTEINS
ACUTE PHASE PROTEINS
1. C-Reactive Protein (CRP)
2. Ceruloplasmin
Wilson's Disease
STRUCTURE OF IMMUNOGLOBULINS
Heavy and Light Chains
Variable and Constant Regions
Different classes of immunoglobulins
1. lmmunoglobulin G (IgG)
2. Immunoglobulin M (IgM)
3. Immunoglobulin A (IgA)
4. Immunoglobulin E (IgE)
PARAPROTEINEMIAS
1. Multiple Myeloma (Plasmacytoma)
2. Bence Jones Proteinuria
3. Hypergammaglobulinemia
14:
Citric Acid Cycle, Biological Oxidation and Electron Transport Chain
BIOLOGICAL OXIDATION
Electron Transport Chain
Energetics of Oxidation Phosphorylation
NAD+-linked Dehydrogenases
FAD-linked Dehydrogenases
HIGH ENERGY COMPOUNDS
Adenosine Triphosphate (ATP)
ORGANIZATION OF ET CHAIN
1. ETC Complex-I
2. Complex II or Succinate-Q-Reductase
3. Co-enzyme Q
4. Complex III or Cytochrome Reductase
5. Cytochrome c
6. Complex IV or Cytochrome Oxidase
Chemi-osmotic Theory
Energetics of ATP Synthesis
Sites of ATP Synthesis
ATP Synthase (5th Complex)
Inhibitors of ATP Synthesis (Table 14.3)
15:
Heme and Hemoglobin
STRUCTURE OF HEMOGLOBIN
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)
Diagnosis of Porphyrias
Acquired Porphyrias
CATABOLISM OF HEME
1. Generation of Bilirubin
2. Transport to Liver
3. Conjugation in Liver
4. Excretion of Bilirubin to bile
5. Fate of Conjugated Bilirubin in Intestine
6. Enterohepatic circulation
7. Final excretion
Plasma Bilirubin
van den Bergh Test for Bilirubin
HYPERBILIRUBINEMIAS
Crigler-Najjar Syndrome
2. Acquired Hyperbilirubinemias
STRUCTURE Of HEMOGLOBIN
TRANSPORT OF OXYGEN BY HEMOGLOBIN
1. Heme-heme Interaction and Co-operativity
2. Effect of pH and pCO2
3. The Bohr Effect
5. Effect of Temperature
6. Effect of 2,3-BPG
TRANSPORT OF CARBON DIOXIDE
1. Dissolved Form
2. Isohydric Transport of Carbon Dioxide
3. Carriage as Carbaminohemoglobin
Fetal Hemoglobin (HbF)
HEMOGLOBIN DERIVATIVES
1. Carboxyhemoglobin (Carbon Monoxy Hb) (CO-Hb)
2-A. Met-hemoglobin (Met-Hb)
2-B. Met-hemoglobinemias
HEMOGLOBIN (GLOBIN CHAIN) VARIANTS
1. Sickle syndromes
2. Structural variations leading to thalassemia
1. Hemoglobin S (HbS)
(Sickle Cell Hemoglobin)
A. Sickle Cell Disease
B. Sickle Cell Trait
2. Hemoglobin E
THALASSEMIAS
1. Beta thalassemia
2. Alpha thalassemias
3. Thalassemia syndromes
MYOGLOBIN (MB)
ANEMIAS
1. Anemias due to Impaired Production of RBCs
2. Hemolytic Anemias due to Intracorpuscular Defect
3. Hemolytic Anemias due to Extracorpuscular Causes
4. Hemorrhage
16:
Vitamins-I: Fat Soluble Vitamins (A, D, E, K)
VITAMIN D (CHOLECALCIFEROL)
1. Formation of Vitamin D
2. Activation of Vitamin D
3. Biochemical Effects of Vitamin D
A. Vitamin D and Absorption of Calcium
B. Effect of Vitamin D in Bone
C. Effect of Vitamin D in Renal Tubules
4. Deficiency of Vitamin D
A. Causes for Vitamin D Deficiency
B. Clinical Features of Rickets
C. Clinical Features of Osteomalacia
5. Requirements of Vitamin D
6. Sources of Vitamin D
7. Hypervitaminosis D
1. Chemical Nature
2. Biochemical Role of Vitamin E
3. Inter-relationship with Selenium
4. Deficiency Manifestations of Vitamin E
5. Sources of Vitamin E
6. Requirement
1. Chemistry of Vitamin K
2. Biochemical Role of Vitamin K
3. Causes for Deficiency of Vitamin K
4. Clinical Manifestations of Deficiency
7. Daily Requirements of Vitamin K
8. Sources of Vitamin K
17:
Vitamins-II: Water Soluble Vitamins (Thiamine, Riboflavin, Niacin, Pyridoxine, Pantothenic Acid, Biotin Folic Acid, Vitamin B12 and Ascorbic Acid)
18:
Mineral Metabolism
CALCIUM (Ca++)
1. Sources of Calcium
2. Daily Requirement of Calcium
A. Absorption of Calcium
B. Factors Affecting Absorption of Calcium
4. Calcium in Cells
5. Functions of Calcium
6. Calcium in Blood
7. Factors Regulating Blood Calcium Level
A. V itamin D
B. P arathyroid Hormone (PTH)
Mechanism of action of PTH
C. Calcitonin
Calcitonin, calcitriol and PTH act together
D. Phosphorus
E. Children
8. Hypercalcemia
9. Hypocalcemia and Tetany
Mild decrease in serum calcium
10. Bone Mineralization and Demineralization
11. Osteoporosis
PHOSPHORUS
Functions of Phosphate Ions
Requirement and Source
Serum Level of Phosphorus
SODIUM (Na+)
Edema
Hypernatremia is seen in
Causes of Hyponatremia
POTASSIUM (K+)
Requirement
Sources
Normal level
Hypokalemia
Hyperkalemia
CHLORIDE (Cl−)
Hyperchloremia is seen in
Causes for Hypochloremia
IRON (Fe)
1. Distribution of iron
2. Requirement of Iron (ICMR, 1990)
3. Sources of Iron
4. Factors Influencing Absorption of Iron
A. Reduced form of iron
B. Ascorbic acid
C. Interfering substances
5. Mucosal Block Theory
6. Iron Transport in Blood
7. Storage of Iron
8. Iron is Conserved
9. Excretion of Iron
10-A. Iron Deficiency Anemia
10-B. Causes for Iron Deficiency
10-C. Microscopic Appearance
10-D. Clinical Manifestations
11. Treatment of Iron Deficiency
12. Iron Toxicity
COPPER (CU)
Functions of Copper
Abnormal Metabolism of Copper
Zinc (ZN)
Zinc Deficiency Manifestations
Requirement of Zinc
HEAVY METAL POISONS
19:
Energy Metabolism and Nutrition
9. IMPORTANCE OF CARBOHYDRATES
A. Dietary Carbohydrates
B. Sucrose
C. Dietary Fiber
10. NUTRITIONAL IMPORTANCE OF LIPIDS
10-A. Cholesterol and Heart Diseases
10-B. Recommended Daily Intake of Fat
11. IMPORTANCE OF PROTEINS
12-A. Nitrogen Balance
B. Factors Affecting Nitrogen Balance
C. Maintenance of Nitrogen Balance
13-A. Nutritional Values (Nutritional Indices) of Proteins
B. Biological Value (BV) of Protein
C. Limiting Amino Acids
G. Supplementation
14. PROTEIN-ENERGY MALNUTRITION
Biochemical Alterations
Treatment of Protein Energy Malnutrition
Sequelae of Protein Calorie Malnutrition
15. OBESITY
Diseases related with obesity
16. PRESCRIPTION OF DIET
A. First Step: Calorie Requirement
B. Second Step: Proximate Principles
C. Third Step: General Composition of Food
Mutual Supplementation of Cereals and Pulses:
16-D. Fourth Step: Determine the Items of Food
20:
Detoxification and Free Radicals
PHASE ONE REACTIONS
1. Oxidative Reactions
2. Reductive Reactions
3. Hydrolysis
PHASE TWO REACTIONS; CONJUGATIONS
1. Glucuronic Acid
2. Sulfate Conjugation
3. Cysteine and Glutathione
4. Acetylation
5. Conjugation with Glycine
6. Methylation Reactions
PHASE THREE REACTIONS
FREE RADICALS
Definition
Generation of Free Radicals
Free Radical Scavenger Enzyme Systems
21:
Acid-base, pH, Electrolyte and Water Balance
ACIDS AND BASES
1. Definition
2. Weak and Strong Acids
3. Dissociation Constant
4. Acidity of a Solution and pH
5. The Effect of Salt Upon the Dissociation
1. Definition
2. Composition of a Buffer
3. Factors Affecting pH of a Buffer
4. Factors Affecting Buffer Capacity
5. How do Buffers Act?
6. Effective Range of a Buffer
ACID-BASE BALANCE
1. Normal pH
2. Acidosis
3. Alkalosis
4. Volatile and Fixed Acids
5. Mechanisms of Regulation of pH
1. BUFFERS OF THE BODY FLUIDS
1-A. Bicarbonate Buffer System
1-B. Alkali Reserve
1-C. Phosphate Buffer System
1-D. Protein Buffer System
1-E. Buffers Act Quickly, But Not Permanently
2. RESPIRATORY REGULATION OF pH
The second line of defence
3. RENAL REGULATION OF pH
3.A. Excretion of H+; Generation of Bicarbonate
B. Excretion of H+ as Titratable Acid
3.D. Excretion of Ammonium Ions
Relationship of pH with K+ion balance
DISTURBANCES IN ACID-BASE BALANCE
ELECTROLYTE AND WATER BALANCE
Intake and Output of Water
Osmolality of Extra Cellular Fluid
Regulation of Sodium and Water Balance
Renin-Angiotensin System
Autoregulation
1. Isotonic Contraction of ECF
2. Hypotonic Contraction
3. Hypertonic Contraction
4. Isotonic Expansion
5. Hypotonic Expansion
6. Hypertonic Expansion
22:
Muscle and Supportive Tissue Proteins
COLLAGEN
Structure of Collagen
Synthesis of Collagen
Hydroxylation of Proline and Lysine
Triple Stranded Helix
Quarter Staggered Arrangement
Cross Links in Collagen Fibers
Functions of collagen
Abnormalities in Collagen
ELASTIN
MUSCLE PROTEINS
Myosin
Actin
23:
Nucleotides: Chemistry and Metabolism
BIOSYNTHESIS OF PURINE NUCLEOTIDES
Step 0 (Preparatory Step), PRPP synthesis
De Novo Synthesis of Purine Nucleotides Steps 1 to 10
Formation of AMP
Conversion of IMP to GMP
Salvage Pathway
Regulation of Purine Synthesis
Analogues as Purine Synthesis Inhibitors
Degradation of Purine Nucleotides
URIC ACID
GOUT
1. Primary Gout
A. 5-phosphoribosyl amido transferase
B. Glucose-6-phosphatase Deficiency
2. Secondary Hyperuricemia
A. Increased production of uric acid
B. Reduced excretion rate
3. Clinical Findings of Gout
Treatment Policies in Gout
Lesch-Nyhan Syndrome
DE NOVO SYNTHESIS OF PYRIMIDINE
Regulation of Pyrimidine Synthesis
Disorders of Pyrimidine Metabolism
Orotic Aciduria
Synthesis of Deoxythymine Nucleotides
24:
DNA—Deoxyribonucleic Acid: Structure and Replication
STRUCTURE OF DNA
Polarity of DNA molecule
Watson-Crick Model of DNA Structure
1. Right handed double helix
2. The base pairing rule
3. Hydrogen bonding
4. Antiparallel
Higher Organisation of DNA
Nucleosomes
Further Condensation of DNA
Chromosomes
DNA is a very big Molecule
Inactivation of DNA During Differentiation
Introns, Exons, Cistrons
REPLICATION OF DNA
Steps of Replication
5. DNA polymerase (DNAP)
A. Bacterial DNA polymerases
B. Mammalian DNA polymerases (DNAP)
6 Initiation of DNA Replication
7. RNA Primer is Required for DNA Synthesis
8. Elongation of DNA strand
9. Discontinuous Synthesis
10. Lagging Strand and Okazaki Pieces
Inhibitors of DNA Replication
25:
Transcription and Translation
RIBONUCLEIC ACID
Central Dogma of Molecular Biology
Replication, Transcription and Translation
Template and Coding Strands
Messenger RNA or mRNA
1. TRANSCRIPTION PROCESS
1-A. Mammalian RNA Polymerases
2. Signals for Initiation of Transcription
PROTEIN BIOSYNTHESIS
1-A. Structure of tRNA Molecule
1-B. Acceptor Arm is at the 3' End
1-C. Anticodon Arm of tRNA
2. Ribosomal RNA (rRNA)
3. Genetic Code
Salient Features of the Genetic Code
i) Triplet Codons
ii) Non-overlapping
iii) Non-punctuated
iv) Degenerate
v) Unambiguous
vi) Universal
vii) Terminator Codons
viii) Initiator Codon
4. TRANSLATION PROCESS
Formation of Initiation Complex
Formation of 80S ribosomal assembly
P and A Sites of Ribosomal Assembly
C. Elongation Process of Translation
i) Binding of New Amino Acyl tRNA
ii) Peptide Bond Formation
iii) Translocation Process
iv) Energy Requirements
D. Termination Process of Translation
E. Post-translational Processing
Inhibitors of Protein Synthesis
i) Reversible Inhibitors in Bacteria
ii) Irreversible Inhibitors in Bacteria
iii) Inhibitors of transcription
26:
Control of Gene Expression
MUTATIONS
1. Classification of Mutations
A. Substitution
B. Deletion
C. Insertion
2. Effects of Mutations
i) Silent Mutation
ii) Mis-sense but Acceptable Mutation
iii) Mis-sense; Partially Acceptable Mutation
iv) Mis-sense; Unacceptable Mutation
v) Nonsense; Terminator Codon Mutation
vi) Frameshift Mutation
vii) Conditional Mutations
3. Mutagens and Mutagenesis
4. Manifestations of Mutations
i) Lethal Mutations
ii) Silent Mutations
iii) Beneficial Mutations
iv) Carcinogenic Effect
CELL CYCLE
REGULATION OF GENE EXPRESSION
1. Operon Concept of Gene Regulation
2. The Lac Operon
3. Transcription is Normally Repressed
4. Derepression of Lac Operon
5. Clinical Applications
6. Regulation of Genes by Repression
7. Hormone Response Elements (HRE)
27:
Recombinant DNA Technology and Gene Therapy
RECOMBINANT DNA TECHNOLOGY
VECTORS
1. Preparation of Chimeric DNA Molecules
2. Cloning of Chimeric DNA
3. Transfection of Vector into the Host
4. Selection
5. Expression Vectors
6. Human Recombinant Proteins
Human Genome Project (HGP)
GENE THERAPY
Summary of the Procedure
How the Genes are Introduced?
The Vectors
5. Accomplishments
28:
AIDS and Cancer
AIDS AND HIV
The Indian Scene
Transmission
Natural Course of the Disease
THE HUMAN IMMUNODEFICIENCY VIRUS
1. Structure
2. Virus Entry
3. Replication of HIV
4. Immunology of AIDS
5. Anti-HIV Drugs
6. Prevention
Etiology of Cancer
Mutagens
Aflatoxins
Cigarette
Antimutagens
ONCOGENIC VIRUSES
ONCOGENES
Oncogenes are normal constituents of cells
Many factors activate oncogenes
Anti-oncogenes or Onco-suppressor Genes
Oncofetal Antigens
TUMOR MARKERS
Clinically important tumor markers
29:
Methods of Separation and Assay of Biological Compounds
ELECTROPHORESIS
1. Factors Affecting Electrophoresis
2. Electrophoresis Apparatus
3. Support Medium for Electrophoresis
A. Filter Paper
B. Cellulose Acetate Membrane
C. Agar or Agarose
4. Visualization of Protein Bands
5. Immunoelectrophoresis
CHROMATOGRAPHY
1. Adsorption Chromatography
2. Partition Chromatography
A. Paper Chromatography
B. Thin Layer Chromatography (TLC)
C. Visualization of Chromatography
D. Importance of Rf Value
HYBRIDIZATION AND BLOT TECHNIQUES
1. Probes
2. DNA-DNA Hybridization
3. Southern Blot Technique
4. Northern Blotting for Identifying RNA
5. Western Blot Analysis for Proteins
RADIOIMMUNOASSAY (RIA)
Advantage of RIA
Disadvantages of RIA
ELISA TEST
Antigen Detection by ELISA Method
Antibody Detection by ELISA
COLORIMETER
SPECTROPHOTOMETER
30:
Liver and Kidney Function Tests
RENAL FUNCTION TESTS
Glomerular Function
Glomerular Filtration Rate (GFR)
Functions of the Tubules
Renal Threshold and Tubular Maximum
Reabsorption of Water
NONPROTEIN NITROGEN (NPN)
MARKERS OF G.F.R.
Definition
Creatinine Clearance Test
Importance of Creatinine Clearance
Normal Serum Creatinine Level
Procedure for Creatinine Clearance Test
Reference values for Creatinine Clearance
Interpretation of Creatinine Clearance
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
A. Pre-renal conditions
B. Renal diseases
C. Post-renal causes
D. Decreased Blood Urea
Inulin Clearance
Diodrast Clearance
MARKERS OF GLOMERULAR PERMEABILITY
TESTS FOR TUBULAR FUNCTION
1. Specific Gravity of Urine
2. Concentration Test
3. Dilution Tests
4. Urinary Acidification
Appendices
Essay Questions and Short Notes
CHAPTER 1: CELL
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CHAPTER 2: AMINO ACIDS AND PROTEINS
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CHAPTER 3: ENZYMOLOGY
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CHAPTER 4: CARBOHYDRATES, CHEMISTRY
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CHAPTER 5: METABOLIC PATHWAYS OF GLUCOSE
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CHAPTER 6: REGULATION OF BLOOD GLUCOSE
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CHAPTER 7: OTHER SUGARS
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CHAPTER 8: SALIVA AND DENTAL CARIES
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CHAPTER 9: LIPIDS, CHEMISTRY
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CHAPTER 10: METABOLISM OF FATTY ACIDS
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CHAPTER 11: CHOLESTEROL
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CHAPTER 12: AMINO ACID METABOLISM
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CHAPTER 13: PLASMA PROTEINS
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CHAPTER 14: CITRIC ACID CYCLE
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CHAPTER 15: HEME AND HEMOGLOBIN
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CHAPTER 16: FAT SOLUBLE VITAMINS
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CHAPTER 17: WATER SOLUBLE VITAMINS
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CHAPTER 18: MINERAL METABOLISM
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CHAPTER 19: NUTRITION
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CHAPTER 20: DETOXIFICATION
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CHAPTER 21: ACID BASE BALANCE
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CHAPTER 23: NUCLEOTIDES
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CHAPTER 24: DNA STRUCTURE, REPLICATION
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CHAPTER 25: TRANSCRIPTION AND TRANSLATION
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CHAPTER 26: CONTROL OF GENE EXPRESSION
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CHAPTER 27: RECOMBINANT DNA TECHNOLOGY
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CHAPTER 28: AIDS AND CANCER
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CHAPTER 29: LABORATORY TECHNIQUES
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CHAPTER 30: LIVER AND KIDNEY FUNCTION TESTS
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INDEX
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