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Textbook of Biochemistry for Dental Students
DM Vasudevan, Sreekumari S, Kannan Vaidyanathan
CHAPTER 1:
Subcellular Organelles and Cell Membranes
INTRODUCTION
BIOMOLECULES
SUBCELLULAR ORGANELLES
Nucleus
Endoplasmic Reticulum (ER)
Golgi Apparatus
Lysosomes
Mitochondria
Plasma Membrane
TRANSPORT MECHANISMS
Simple Diffusion
Facilitated Diffusion
Ion Channels
Amelogenin
Active Transport
Uniport, Symport and Antiport
ENDOCYTOSIS
Receptor Mediated Endocytosis
Phagocytosis
A QUICK LOOK
CHAPTER 2:
Amino Acids and Proteins
CLASSIFICATION OF AMINO ACIDS
Based on Structure
A. Aliphatic amino acids
B. Aromatic amino acids
C. Heterocyclic amino acids
D. Imino acid
E. Derived amino acids
2. Classification Based on Side Chain
3. Classification Based on Metabolic Fate
4. Classification Based on Nutritional Requirement
Naming of Carbon Atoms
PROPERTIES OF AMINO ACIDS
Isoelectric Point
Optical Activity
Reactions due to Carboxyl Group
Decarboxylation
Amide Formation
Reactions due to Amino Group
Transamination
Oxidative Deamination
Reactions due to Side Chains
Ester Formation by OH Group
Reaction of the Amide Group
Reactions of SH Group
Special Functions of Amino Acids
Color Reactions of Amino Acids and Proteins
Peptide Bond
STRUCTURE OF PROTEINS (ORGANIZATION OF PROTEINS)
Primary Structure; sequence
Numbering of Amino Acids in Proteins
Primary Structure of Insulin
Primary Structure Determines Activity
Secondary Structure of Proteins
Alpha helix
Beta-pleated sheet
Tertiary Structure
Quaternary Structure
Structure-Function Relationship
Hemoglobin
Collagen
Keratin
PHYSICAL PROPERTIES OF PROTEINS
ISOELECTRIC PH (PI) OF PROTEINS
PRECIPITATION REACTIONS
Salting Out
Isoelectric Precipitation
Precipitation by Organic Solvents
Precipitation by Heavy Metal Ions
Anionic or Alkaloidal Reagents
DENATURATION OF PROTEINS
HEAT COAGULATION
CLASSIFICATION OF PROTEINS
1. Classification based on Functions
2. Classification based on Solubility
Simple Proteins
Conjugated Proteins
Derived Proteins
3. Classification based on Nutritional value
Nutritionally rich proteins
Incomplete proteins
Poor proteins
Related Topics
A QUICK LOOK
CHAPTER 3:
Enzymology
CLASSIFICATION OF ENZYMES
IUBMB system of nomenclature of enzymes
COENZYMES
First Group of Coenzymes
Nicotinamide Adenine Dinucleotide (NAD+)
Second Group of Coenzymes
Adenosine Triphosphate (ATP)
Salient features of Coenzymes
Metalloenzymes
MODE OF ACTION OF ENZYMES
1. Lowering of Activation Energy
2. Michaelis-Menten Theory
Fischer's Template Theory
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
FACTORS INFLUENCING ENZYME ACTIVITY
1. Enzyme Concentration
2. Substrate Concentration
Michaelis Constant
Definition of Km
3. Effect of Concentration of Products
4. Effect of Temperature
5. Effect of pH
ENZYME ACTIVATION
Covalent Modification
ENZYME INHIBITION
1. Competitive Inhibition
Clinical Significance
2. Noncompetitive Inhibition
3. Allosteric Regulation
Key Enzymes
Induction
Repression
ISOENZYMES
CLINICAL ENZYMOLOGY
Lactate Dehydrogenase (LDH)
Isoenzymes of LDH
Creatine Kinase (CK)
CK and Muscle Diseases
Isoenzymes of CK
ALANINE AMINOTRANSFERASE (ALT)
Alkaline Phosphatase (ALP)
Acid Phosphatase (ACP)
A QUICK LOOK
CHAPTER 4:
Carbohydrates–I: Chemistry
FUNCTIONS OF CARBOHYDRATES
NOMENCLATURE
STEREOISOMERS
D and L isomerism of glucose
Diastereoisomers 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. Glycosides
8. Formation of Esters
9. Amino Sugars
10. Deoxy Sugars
11. Pentoses
DISACCHARIDES
1. Sucrose
2. Lactose
3. Maltose
POLYSACCHARIDES
1. Starch
2. Glycogen
3. Cellulose
4. Inulin
HETEROGLYCANS
1. Agar
2. Mucopolysaccharides
Hyaluronic Acid
Heparin
GLYCOPROTEINS AND MUCOPROTEINS
DIGESTION OF CARBOHYDRATES
Lactose Intolerance
ABSORPTION OF CARBOHYDRATES
1. Cotransport from Lumen to Intestinal Cell
2. Release of Glucose into Blood
3. GluT2 in Other Tissues
4. GluT4 in Muscle and Adipose Tissue
A QUICK LOOK
CHAPTER 5:
Carbohydrates–II: Major Metabolic Pathways of Glucose
GLUCOSE METABOLISM
Importance of Glucose
GLYCOLYSIS (EMBDEN-MEYERHOF PATHWAY)
Importance of the Pathway
Step 0: 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
Steps 5 and 10 are Coupled
Energy Yield from Glycolysis
CORI's CYCLE OR LACTIC ACID CYCLE
Regulation of Glycolysis
1. Hormones
2. Phosphofructokinase (PFK)
3. Pyruvate Kinase
METABOLIC FATE OF PYRUVATE
Pyruvate Dehydrogenase Complex
Pyruvate as a Junction Point
GLUCONEOGENESIS
1. Pyruvate Carboxylase Reaction
2. Phosphoenolpyruvate Carboxykinase
3. Reversal of Glycolysis
4. Fructose-1,6-bisphosphatase
5. Glucose-6-phosphatase
Energy Requirement for Gluconeogenesis
Substrates for Gluconeogenesis
1. Lactate
2. Glucogenic amino acids
Regulation of Gluconeogenesis
1. Hormonal Regulation of Gluconeogenesis
2. Physiological Significance
GLYCOGEN METABOLISM
Functions of Glycogen
Degradation of Glycogen (Glycogenolysis)
1. Glycogen Phosphorylase
2. Debranching Needs Two Enzymes
3. Phosphoglucomutase
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
Generation of Cyclic AMP (cAMP)
Regulation
GLYCOGEN STORAGE DISEASES
Glycogen Storage Disease Type-I
A QUICK LOOK
CHAPTER 6:
Carbohydrates–III: Regulation of Blood Glucose: Diabetes Mellitus
Regulation of blood glucose
Factors Maintaining Blood Sugar
Post-prandial Regulation
Regulation in Fasting State
NORMAL PLASMA GLUCOSE LEVEL
Sugar in Urine
Determination of Glucose in Body Fluids
Enzymatic Method
Effect of food on Glucose Level
ORAL GLUCOSE TOLERANCE TEST (OGTT)
Normal Values and Interpretations
Diagnostic Criteria for Diabetes Mellitus
Causes for Abnormal GTT Curve
1. Impaired Glucose Tolerance (IGT)
2. Gestational Diabetes Mellitus (GDM)
3. Alimentary Glucosuria
4. Renal Glucosuria
REDUCING SUBSTANCES IN URINE
Differential Diagnosis of Reducing Substances in Urine
1. Hyperglycemic Glucosuria
2. Fructosuria
3. Lactosuria
4. Galactosuria
5. Pentosuria
6. Non-carbohydrate Reducing Compounds
IDENTIFICATION OF REDUCING SUGARS
Benedict's test
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. Glycohemoglobin (HbA1c) estimation
Management of Diabetes Mellitus
A QUICK LOOK
CHAPTER 7:
Carbohydrates—IV: Minor Metabolic Pathways of Carbohydrates
HEXOSE MONOPHOSPHATE (HMP) SHUNT 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. Methemoglobinemia
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
A QUICK LOOK
CHAPTER 8:
Lipids–I: Chemistry of Fats
CLASSIFICATION OF LIPIDS
I. Simple Lipids
II. Compound Lipids
Phospholipids, containing phosphoric acid.
Non-phosphorylated lipids
III. Derived Lipids
IV. Lipids Complexed to Other Compounds
FATTY ACIDS
CLASSIFICATION OF FATTY ACIDS
SATURATED FATTY ACIDS
UNSATURATED FATTY ACIDS
Clinical significance of PUFA
PROPERTIES OF FATTY ACIDS
1. Hydrogenation
2. Halogenation
3. Melting point
4. Salt formation
5. Ester formation
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
PHOSPHOLIPIDS
A. Phosphatidates
B. Amphipathic Nature
D. Biomembranes
1. Phosphatidylcholine or Lecithin
2. Phosphatidyl ethanolamine or Cephalin
3. Sphingolipids
Phosphosphingosides
NON-PHOSPHORYLATED LIPIDS
Lipoproteins
LIPID STORAGE DISEASES OR SPHINGOLIPIDOSES
Essential Fatty Acids
Eicosanoids
PROSTAGLANDINS (PGs)
Biosynthesis of Prostaglandins
Regulation of Synthesis
Biological Actions
A QUICK LOOK
CHAPTER 9:
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
ABSORPTION OF LIPIDS
Absorption of Long Chain Fatty Acids
1. Mixed micelle formation
2. Enterohepatic Circulation of Bile Salts
3. Re-esterification inside the Mucosal Cell
3. Chylomicrons
4. SCFA Absorption is Different
5. Abnormalities in Absorption of Lipids
6. Fate of absorbed fat
BETA-OXIDATION OF FATTY ACIDS
Preparative step for beta-oxidation
Preparative step 1: Activation of Fatty Acids
Preparative step 2: Role of Carnitine
Preparative step 3: Carnitine Acyltransferase
Clinical Applications
Beta-oxidation steps
Energetics of beta-oxidation (ATP Yield)
Regulation of Beta-oxidation
OXIDATION OF ODD CHAIN FATTY ACIDS
Propionate is Gluconeogenic
DE NOVO SYNTHESIS OF Fatty acids
Fatty Acid Synthase (FAS) Complex
Summary of de novo Synthesis
Coenzymes of Fatty Acid Synthesis
Regulation of Fatty Acid Synthesis
SYNTHESIS OF TRIGLYCERIDES (TAG)
Obesity
Role of Liver in Fat Metabolism
Liver–Adipose Tissue Axis
FATTY LIVER AND LIPOTROPIC FACTORS
Causes of Fatty Liver
5. Fatty liver progresses to cirrhosis
Lipotropic Factors
METABOLISM OF KETONE BODIES
A. Ketogenesis
B. Ketolysis
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. Diabetes, Starvation, Ketosis, Cholesterol
D. Consequences of Ketosis
E. Diagnosis of Ketosis
F. Differential Diagnosis
G. Management of Ketoacidosis
A QUICK LOOK
CHAPTER 10:
Lipids–III: Cholesterol, Lipoproteins and Cardiovascular Diseases
SIGNIFICANCE AND FUNCTIONS OF CHOLESTEROL
Structure of Cholesterol
BIOSYNTHESIS OF CHOLESTEROL
Regulation of Cholesterol Synthesis
Excretion of Cholesterol
PLASMA LIPIDS
Carriage of Cholesterol in Blood
Classification of Lipoproteins
Chylomicrons
General Characteristics of Lipoproteins
Apolipoproteins
1. CHYLOMICRONS
Insulin increases LpL activity
2. Very low density lipoproteins
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 lifestyle
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
A QUICK LOOK
CHAPTER 11:
Amino Acid Metabolism
Digestion of proteins
A. Gastric Digestion of Proteins
1. Rennin
2. Pepsin
B. Pancreatic Digestion of Proteins
1. Trypsin
2. Chymotrypsin
3. Carboxypeptidases
C. Intestinal Digestion of Proteins
Absorption of Amino Acids
Clinical Applications
GENERAL METABOLISM OF AMINO ACIDS
FORMATION OF AMMONIA
A. Transamination
Biological Significance of Transamination
1. First step of catabolism
2. Synthesis of non-essential amino acids
Clinical Significance of Transamination
B. Transdeamination
DISPOSAL/DETOXIFICATION OF AMMONIA
1. First line of Defense (Trapping of ammonia)
2. 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
Regulation of the Urea Cycle
Disorders of Urea Cycle
Urea Level in Blood and Urine
GLYCINE (GLY) (G)
1. Glycine Cleavage System
2. Special Metabolic Functions of Glycine
3. Creatine and Creatine Phosphate
Clinical Applications
4. Glycine as a Conjugating Agent
Methionine (Met) (M)
Functions of Cysteine
Metabolic Functions of Glutathione
Homocystinuria
PHENYLALANINE (PHE) (F) AND TYROSINE (TYR) (T)
Phenylalanine to Tyrosine
Catabolism of Tyrosine (and Phenylalanine)
Important Specialized Products from Tyrosine
1. Synthesis of melanin
2. Synthesis of Catecholamines
Actions of Epinephrine (Adrenaline)
Degradation of Adrenaline
PHENYL KETONURIA (PKU)
Laboratory Diagnosis
Treatment of Phenylketonuria
ALKAPTONURIA
ALBINISM
TRYPTOPHAN (TRP) (W)
Nicotinic Acid Pathway of Tryptophan
Serotonin
Functions of Serotonin
Carcinoid Tumors
Melatonin
HISTIDINE (HIS) (H)
Histamine
Biogenic Amines
Fate of Carbon skeletons of amino acids
ONE-CARBON METABOLISM
Generation of One-Carbon Groups
Interconversion of One-Carbon Groups
Utilization of One-carbon Groups
Inborn Errors of Metabolism
Inborn Errors Associated with Protein Metabolism
Inborn Errors Associated with Carbohydrate Metabolism are
A QUICK LOOK
CHAPTER 12:
Plasma Proteins
ELECTROPHORESIS
Normal Values and Interpretations
Abnormal Patterns in Clinical Diseases
ALBUMIN
Functions of Albumin
1. Colloid osmotic pressure of plasma
2. Transport Function
3. Nutritional function
4. Blood brain barrier
5. Edema
Albumin-Globulin Ratio
TRANSPORT PROTEINS
ACUTE PHASE PROTEINS
1. C-Reactive Protein (CRP)
2. Ceruloplasmin and Wilson's Disease
STRUCTURE OF IMMUNOGLOBULINS
Heavy and Light Chains
Variable and Constant Regions
Different Classes of Immunoglobulins
1. Immunoglobulin 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
A QUICK LOOK
CHAPTER 13:
Tricarboxylic Acid Cycle and Biological Oxidation
REACTIONS OF THE CYCLE
Preparatory Steps
1st Step: Formation of citric acid
2nd Step: Formation of isocitrate
3rd Step: Formation of Alpha Ketoglutarate
4th Step: Formation of Succinyl-CoA
5th Step: Generation of Succinate
6th Step: Formation of Fumarate
7th Step: Formation of Malate
8th Step: Regeneration of Oxalo-acetate
SIGNIFICANCE OF TCA CYCLE
1. Complete Oxidation of Acetyl-CoA (CO2 Removal Steps)
2. ATP Generating Steps in TCA Cycle
3. Final Common Oxidative Pathway
4. Integration of Major Metabolic Pathways
5. Excess carbohydrates are converted as fat
6. No Net Synthesis of Carbohydrates from Fat
7. Amphibolic Pathway
8. Anaplerotic Role of TCA Cycle
REGULATION OF THE CITRIC ACID CYCLE
Inhibitors of TCA Cycle
Stages of oxidation of foodstuffs
First stage
Second stage
Third stage
REDOX POTENTIALS
Substrate Level Phosphorylation
Biological Oxidation
Electron Transport Chain
Energetics of Oxidation Phosphorylation
NAD+ linked dehydrogenases
FAD-linked Dehydrogenases
HIGH ENERGY COMPOUNDS
Adenosine Triphosphate (ATP)
ORGANIZATION OF ELECTRON TRANSPORT CHAIN
Sites of ATP Synthesis
Chemiosmotic Theory
ATP Synthase (5th Complex)
Energetics of ATP Synthesis
Inhibitors of ATP Synthesis
A QUICK LOOK
CHAPTER 14:
Heme and Hemoglobin
STRUCTURE OF HEMOGLOBIN
Structure of Heme
Biosynthesis 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
1. Congenital Hyperbilirubinemias
Crigler Najjar Syndrome
2. Acquired Hyperbilirubinemias
Physiological Jaundice
3. Hemolytic Jaundice
Hemolytic Disease of the Newborn
Hemolytic Diseases of Adults
4. Hepatocellular Jaundice
5. Obstructive Jaundice
STRUCTURE Of HEMOGLOBIN
TRANSPORT OF oxygen BY HEMOGLOBIN
Oxygen Dissociation Curve (ODC)
1. Heme-heme Interaction and Cooperativity
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 Carbamino-Hemoglobin
Fetal Hemoglobin (HbF)
HEMOGLOBIN DERIVATIVES
1. Carboxy-Hemoglobin (Carbon Monoxy Hb) (CO-Hb)
2A. Methemoglobin (MetHb)
2B. Methemoglobinemias
HEMOGLOBIN (GLOBIN CHAIN) VARIANTS HEMOGLOBINOPATHIES
1. Hemoglobin S (Hb S) (Sickle Cell Hemoglobin)
1A. Sickle Cell Disease
1B. Sickle Cell Trait
2. Hemoglobin E
THALASSEMIAS
Beta Thalassemia
Thalassemia Syndromes
MYOGLOBIN (MB)
ANEMIAS
A QUICK LOOK
CHAPTER 15:
Fat Soluble Vitamins
VITAMIN A
Chemistry
Absorption of Vitamin A
Transport from Liver to Tissues
Uptake by Tissues
Biochemical Role of Vitamin A
Wald's Visual Cycle
Regeneration of 11-cis-retinal
Dark Adaptation Mechanism
Rods are for Vision in Dim Light
Cones are for Color Vision
Biochemical Functions of Vitamin A
Deficiency Manifestations of Vitamin A
Causes for Vitamin A Deficiency
Dietary Sources of Vitamin A
Daily Requirements 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 in Bone
Effect of Vitamin D in Renal Tubules
Deficiency of Vitamin D
Causes for Vitamin D Deficiency
Clinical Features of Rickets
Clinical Features of Osteomalacia
Requirements of Vitamin D
Sources of Vitamin D
Hypervitaminosis D
VITAMIN E
Chemical Nature
Biochemical Role of Vitamin E
Interrelationship with Selenium
Deficiency Manifestations of Vitamin E
Sources of Vitamin E
Requirement
VITAMIN K
Chemistry of Vitamin K
Biochemical Role of Vitamin K
Causes for Deficiency of Vitamin K
Clinical Manifestations of deficiency
Daily Requirements of Vitamin K
Sources of Vitamin K
A QUICK LOOK
CHAPTER 16:
Water Soluble Vitamins
B COMPLEX GROUP OF VITAMINS
THIAMINE (VITAMIN B1)
Sources
Physiological Role of Thiamine
Deficiency Manifestations of Thiamine
Recommended Daily Allowance of Thiamine
RIBOFLAVIN (VITAMIN B2)
Structure of Riboflavin
Coenzyme Activity of Riboflavin
Riboflavin Deficiency
Dietary Sources of Riboflavin
Daily Requirement
NIACIN
Chemistry of Niacin
One Hydrogen Atom and One Electron
NAD+ Dependent Enzymes
NADPH Reactions
Niacin Deficiency
Niacin is Synthesized from Tryptophan
Causes for Niacin Deficiency
Dietary Sources of Niacin
Recommended Daily Allowance (RDA)
VITAMIN B6
Coenzyme Form
Functions of Pyridoxal Phosphate
Deficiency Manifestations of Pyridoxine
Dietary Sources
Requirement of B6
PANTOTHENIC ACID
Structure
Coenzyme Activity of Pantothenic Acid
Deficiency of Pantothenic Acid
Sources of Pantothenic Acid
Requirement of Pantothenic Acid
BIOTIN
Biotin Requiring CO2 Fixation Reactions
Propionyl-CoA carboxylase
Pyruvate Carboxylase
Biotin-Independent Carboxylation Reactions
Biotin Antagonists
Requirement of Biotin
Sources of Biotin
FOLIC ACID
Chemistry of Folic Acid
Coenzyme Functions of Folic Acid
Causes for Folate Deficiency
Deficiency Manifestations
Sources of Folic Acid
Recommended Daily Allowance (RDA)
Folate Antagonists
VITAMIN B12
Chemistry
Absorption of Vitamin B12
Functional Role of B12
Causes of B12 Deficiency
Deficiency Manifestations
Requirement of Vitamin B12
Dietary Sources
ASCORBIC ACID (VITAMIN C)
Chemistry of Vitamin C
Biosynthesis of Ascorbic Acid in Animals
Excretion of Ascorbic Acid
Biochemical Functions of Vitamin C
Deficiency Manifestations of Vitamin C
Dietary Sources of Vitamin C
Requirement of Vitamin C
Therapeutic Use of Vitamin C
A QUICK LOOK
CHAPTER 17:
Mineral Metabolism
CALCIUM (CA++)
1. Sources of Calcium
2. Daily Requirement of Calcium
3. Absorption of Calcium
Functions of Calcium
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
Phosphorus
Children
Hypercalcemia
Hypocalcemia and Tetany
Bone Mineralization and Demineralization
Osteoporosis
Paget's Disease
Markers of Bone Diseases
Osteocalcin
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)
Distribution of Iron
Requirement of Iron (ICMR, 1990)
Sources of Iron
Factors Influencing Absorption of Iron
Mucosal Block Theory
Regulation of Absorption
Iron Transport in Blood
Storage of Iron
Iron is Conserved
Excretion of Iron
Iron Deficiency Anemia
Causes for Iron Deficiency
Manifestations of Iron Deficiency Anemia
Treatment of Iron Deficiency
Iron Toxicity
COPPER (Cu)
Functions of Copper
Abnormal Metabolism of Copper
Zinc (Zn)
Zinc Deficiency Manifestations
Requirement of Zinc
IODINE (I)
HEAVY METAL POISONS
Lead Poisoning
A QUICK LOOK
CHAPTER 18:
Nutrition
IMPORTANCE OF CARBOHYDRATES
Dietary Carbohydrates
Sucrose
Dietary Fiber
NUTRITIONAL IMPORTANCE OF LIPIDS
Cholesterol and Heart Diseases
Recommended Daily Intake of Lipids
Importance of Proteins
Nitrogen Balance
Factors Affecting Nitrogen Balance
Maintenance of Nitrogen Balance
Nutritional Values (Nutritional Indices)
Limiting Amino Acids
Supplementation
PROTEIN–ENERGY MALNUTRITION
Biochemical Alterations
Treatment of Protein Energy Malnutrition
OBESITY
Diseases Related with Obesity
PRESCRIPTION OF DIET
First Step: Calorie Requirement
Second Step: Proximate Principles
Third Step: General Composition of Food
Mutual Supplementation of Cereals and Pulses
Fourth Step: Determine the Items of Food
A QUICK LOOK
CHAPTER 19:
Detoxification
PHASE ONE REACTIONS
Oxidative Reactions
Reductive Reactions
Hydrolysis
Phase Two Reactions; Conjugations
Glucuronic Acid
Sulfate Conjugation
Cysteine and Glutathione
Acetylation
Conjugation with Glycine
Methylation Reactions
FREE RADICALS
Generation of Free Radicals
Free Radical Scavenger Enzyme Systems
Damage Produced by Reactive Oxygen Species
Clinical Significance
Antioxidants
A QUICK LOOK
CHAPTER 20:
Acid–Base Balance
ACIDS AND BASES
Definition
Weak and Strong Acids
Acidity of a Solution and pH
Henderson-Hasselbalch Equation
BUFFERS
Definition
Composition of a Buffer
Factors Affecting pH of a Buffer
Factors Affecting Buffer Capacity
How do Buffers Act?
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
Buffers Act Quickly, But Not Permanently
RESPIRATORY REGULATION OF PH
The Second Line of Defense
RENAL REGULATION OF PH
Excretion of H+; Generation of Bicarbonate
Reabsorption of Bicarbonate
Excretion of H+ as Titratable Acid
Excretion of Ammonium Ions
Relationship of pH with K+ Ion Balance
Classification of Acid–Base Disturbances
Acidosis (fall in pH)
Alkalosis (rise in pH)
Compensatory Responses
Mixed Responses
Metabolic Acidosis
Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis
Normal Serum Electrolyte Values (Box 20.5)
ELECTROLYTE AND WATER BALANCE
Intake and Output of Water
Osmolality of Extracellular Fluid
Regulation of Sodium and Water Balance
Renin-Angiotensin System
Autoregulation
Disturbances in Fluid and Electrolyte Balance
A QUICK LOOK
CHAPTER 21:
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
Keratins
MUSCLE PROTEINS
Myosin
Actin
A QUICK LOOK
CHAPTER 22:
Biochemistry of Teeth and Caries
COMPOSITION OF TEETH
Inorganic Components
Trace Elements
Organic Components
Collagen
Other Proteins in Teeth
Proteins of Dentine
Proteins of Enamel
Mineralization
DENTAL CARIES
Microbiological Organisms cause Dental Caries
Streptococcus mutans
Sucrose and Caries
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
A QUICK LOOK
CHAPTER 23:
Nucleotides
BIOSYNTHESIS OF PURINE NUCLEOTIDES
Step 0 (Preparatory Step), PRPP synthesis
De Novo Synthesis of Purine Nucleotides
Formation of AMP
Conversion of IMP to GMP
SALVAGE PATHWAY
Regulation of Purine Synthesis
Analogues as Purine Synthesis Inhibitors
Degradation of Purine Nucleotides
Caffeine
URIC ACID
DISORDERS OF PURINE METABOLISM
GOUT
1. Primary Gout
2. Secondary Hyperuricemia
Increased Production of Uric Acid
Reduced Excretion Rate
3. Clinical Findings of Gout
Treatment Policies in Gout
Lesch-Nyhan Syndrome
Hypouricemia
Adenosine Deaminase (ADA) Deficiency
DE NOVO SYNTHESIS OF PYRIMIDINE NUCLEOTIDES
Regulation of Pyrimidine Synthesis
Disorders of Pyrimidine Metabolism
Orotic Aciduria
Synthesis of Deoxythymine Nucleotides
Anticancer Agents Acting on Pyrimidines
Degradation of Pyrimidine Nucleotides
A QUICK LOOK
CHAPTER 24:
DNA, 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
5. The spiral has a pitch of 3.4 nanometers per turn.
6. Within a single turn, 10 base pairs are seen. Thus, adjacent bases are separated by 0.34 nm.
Other Features
Higher Organization of DNA
Nucleosomes
Further Condensation of DNA
Chromosomes
DNA is a Very Long Molecule
Introns, Exons, Cistrons
REPEAT SEQUENCES OF DNA
Replication of DNA
Meselson-Stahl Experiment (1958)
Steps of Replication
DNA polymerase (DNAP)
Bacterial DNA Polymerases
Mammalian DNA Polymerases
Initiation of DNA Replication
RNA Primer is Required for DNA Synthesis
Elongation of DNA strand
Discontinuous Synthesis
Lagging Strand and Okazaki Pieces
Modifications after Replication
Inhibitors of DNA Replication
DNA REPAIR MECHANISMS
Exonucleolytic Proofreading
Mismatch Repair
Nucleotide Excision Repair (NER)
Base Excision Repair (BER)
Diseases Associated with DNA Repair
Telomere and Telomerase
A QUICK LOOK
CHAPTER 25:
Transcription, Translation
RIBONUCLEIC ACID
Cellular RNAs are of five types
Central Dogma of Molecular Biology
Replication, Transcription and Translation
Template and Coding Strands
Messenger RNA or mRNA
Promoters
TRANSCRIPTION PROCESS
Mammalian RNA Polymerases
1. Initiation of Transcription
Signals for Initiation of Transcription
2. Elongation Process
3. Termination of Transcription
4. Post-transcriptional Processing
Inhibitors of RNA Synthesis
Reverse Transcriptase
Inhibitors of RNA Synthesis
PROTEIN BIOSYNTHESIS
1. Transfer RNA (tRNA) or (sRNA)
Structure of tRNA Molecule
2. Ribosomal RNA (rRNA)
3. Genetic Code
TRANSLATION PROCESS
1. Activation of Amino Acid
2. Initiation of Protein Synthesis
3. Elongation Process of Translation
4. Termination Process of Translation
5. Post-translational Processing
Inhibitors of Protein Synthesis
Genomics and Proteomics
A QUICK LOOK
CHAPTER 26:
Gene Expression
MUTATIONS
1. Classification of Mutations
A. Substitution
B. Deletion
C. Insertion
2. Effects of Mutations
3. Mutagens and Mutagenesis
Site-directed Mutagenesis
CELL CYCLE
REGULATION OF GENE EXPRESSION
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)
A QUICK LOOK
CHAPTER 27:
Molecular Biology Techniques
RECOMBINANT DNA TECHNOLOGY
Applications of Recombinant Technology
1. Quantitative Preparation of Biomolecules
2. Risk of Contamination is Eliminated
3. Specific Probes for Diagnosis of Diseases
4. Gene Therapy
Restriction Endonucleases (RE)
Restriction Sites
Restriction Map
VECTORS
Procedure of DNA Recombination
1. Preparation of 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
Obstacles to Success
STEM CELLS
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
POLYMERASE CHAIN REACTION (PCR)
Clinical Applications of PCR
A QUICK LOOK
CHAPTER 28:
Laboratory Techniques
ELECTROPHORESIS
Factors Affecting Electrophoresis
Electrophoresis Apparatus
Cellulose Acetate Membrane
Agar or Agarose
Visualization of Protein Bands
Immunoelectrophoresis
CHROMATOGRAPHY
Partition Chromatography
Paper Chromatography
Thin Layer Chromatography (TLC)
Visualization of Chromatography
Importance of Rf Value
ELISA TEST
Antibody Detection by ELISA
Antigen Detection by ELISA Method
COLORIMETER
SPECTROPHOTOMETER
A QUICK LOOK
CHAPTER 29:
AIDS, Cancer
AIDS AND HIV
The Indian Scene
Transmission
Natural Course of the Disease
1. Window Period
2. Seropositive Stage
3. AIDS Disease
Pathology of HIV and AIDS
Structure of Virus
Virus Entry
Replication of HIV
Immunology of AIDS
Laboratory Diagnosis
Anti-HIV Drugs
Prevention
CANCER
Etiology of Cancer
Mutagens
Aflatoxins
Cigarette
Antimutagens
ONCOGENIC VIRUSES
ONCOGENES
Oncogenes are Normal Constituents of Cells
Many Factors Activate Oncogenes
Antioncogenes or Oncosuppressor Genes
Oncofetal Antigens
TUMOR MARKERS
Clinically Important Tumor Markers
A QUICK LOOK
CHAPTER 30:
Liver Function Test and Renal Function Test
RENAL FUNCTION TESTS
Glomerular Function
Glomerular Filtration Rate (GFR)
Functions of the Tubules
Renal Threshold
Reabsorption of Water
Nonprotein Nitrogen (NPN)
Markers of GFR
Clearance Tests
Definition
Creatinine Clearance Test
Importance of Creatinine Clearance
Creatinine Clearance Test
Reference Values for Creatinine Clearance
Interpretation of Creatinine Clearance
Urea Clearance Test
Blood Urea Level
A. Prerenal conditions
B. Renal diseases
C. Postrenal causes
MARKERS OF GLOMERULAR PERMEABILITY
TESTS FOR TUBULAR FUNCTION
Specific Gravity of Urine
Concentration Test
Dilution Tests
Urinary Acidification
A QUICK LOOK
CHAPTER 31:
Hormones
INTRODUCTION
1. Hormones Acting through Cyclic AMP (cAMP)
Signal Transduction through G Protein
G protein Activates Adenyl Cyclase
Subunit Activation of G Protein
Inactivation
Second Messenger Activates Protein Kinases
Protein Kinase Phosphorylates the Enzymes
Phosphatases
2. Action of Hormones Acting through Calcium
3. Hormones Acting through PIP2 Cascade
4. Role of Cyclic GMP
6. Hormones with Intracellular Receptors
ADRENAL CORTICAL HORMONES
Synthesis of Steroid Hormones
Secretion of Adrenal Hormones
Biological Effects of Glucocorticoids
Assessment of Glucocorticoid Secretion
Basal Level of Cortisol
Estimation of Urinary Free Cortisol
Plasma ACTH
Assessment of Adrenal Androgen Secretion
Adrenal Hyperfunction
Adrenal Hypofunction
SEX HORMONES
Ovarian Hormones
Regulation of Ovarian Hormones
Testicular Hormones
THYROID HORMONES
Synthesis of Thyroxine
Uptake of Iodine
Oxidation of Iodine
Iodination
Coupling
Storage
Release
Salvage of Iodine
Transport of Thyroid Hormones
Mechanism of Action of Thyroid Hormone
Metabolic Effects of Thyroid Hormones
Assessment of Thyroid Function
Assay of Hormones
Free T3 and T4
Plasma TSH
Detection of Thyroid Antibodies
Abnormalities of Thyroid Function
Hyperthyroidism
Hypothyroidism
Euthyroid Goiter
INSULIN
Structure of Insulin
Biosynthesis of Insulin
Factors Increasing Insulin Secretion
Physiological Actions of Insulin (Mechanisms of Action of Insulin, Metabolic Effects of Insulin)
Insulin Receptors
Uptake of Glucose by Tissues
Utilization of Glucose
Hypoglycemic Effect
Lipogenesis
Antilipolytic Effect
Antiketogenic Effect
HYPERGLYCEMIC HORMONES
GLUCAGON
Physiological Actions of Glucagon
Other Important Hormones
A QUICK LOOK
CHAPTER 32:
Appendices: Appendix I
ABBREVIATIONS USED IN THIS BOOK
APPENDIX II
APPENDIX III
APPENDIX IV
INDEX
TOC
Index
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