118. Disorders Of Lipid Metabolism

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118. Disorders Of Lipid Metabolism

 

 

CATEGORY: Diet Nutrition Supplementation – 500 Courses

COURSE NUMBER: 118

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Syllabus

Introduction ………………………………………. 1
Chapter 1
Disorders of Lipid Digestion and Absorption ……………… 7
1.1. Introduction to the Structures and Properties of Lipids ……. 7
1.2. Digestion and Absorption of Lipids …………………. 18
1.2.1. Lingual and Gastric Digestion………………………………….. 18
1.2.2. Intestinal Digestion ………………………. 19
1.3. Characteristics of Disorders of Lipid Digestion
and Absorption ………………………………… 27
References …………………………………… 30
Chapter 2
Disorders of Fatty Acid Metabolism 31
2.1. General Aspects of Fatty Acid Metabolism ……………. 31
2.1.1. Oxidation of Fatty Acids …………………… 32
2.1.2. Role of Carnitine ………………………… 34
2.1.3. Deficiency of CAT-I and Carnitine…………………..34
2.2. f3 Oxidation of Fatty Acids ……………………….. 34
2.3. Disorders of Propionic Acid Metabolism ……………… 36
2.3.1. Propionyl-CoA Carboxylase Deficiency ………… 37
2.3.2. Methylmalonic Acid Acidemias ……………… 37
2.4. a and w Oxidation of Fatty Acids ………………….. 38
2.5. Refsum’s Disease………………………. 38
2.6. Zellweger’s Syndrome……………………………… 38
2.7. Ketogenesis, Ketosis, and Ketoacidosis ………………. 39
2.8. Synthesis of Fatty Acids …………………………. 43
2.8.1. Elongation of Fatty Acids ………………….. 45
2.8.2. Formation of Nonessential Monoenoic and Polyenoic
Fatty Acids ……………………………45
2.9. Essential Fatty Acid Deficiency …………………….46
References ……………………………………47

Chapter 3
Disorders of Excessive Alcohol Intake: Hypoglycemia, Fatty
Liver, and Liver Cirrhosis …………………………..49
3.1. Introduction to the Biochemical Effects of Alcohol Intake…..49
3.2. Metabolism of Alcohol …………………………..50
3.3. Effects of Alcohol Intake on Fatty Acid Metabolism ……..54
3.4. Alcoholic Hypoglycemia ………………………….55
3.5. Alcoholic Hepatitis and Liver Cirrhosis ……………….55
3.6. Effects of Alcohol on the CNS ……………………..57
3.7. Effects of Acetaldehyde …………………………..59
3.8. Effects of Alcohol on the Heart …………………….59
3.9. Alcohol-Drug Interactions ………………………..59
3.10. Alcohol Withdrawal Symptoms ……………………..60
3.11. Alcohol Intake and Heart Disease ……………………61
References…………………61
Chapter 4
Disorders of Cholesterol Metabolism: Cholesterol

Storage Diseases …………………………………. 63
4.1. Overall Cholesterol Balance in Humans ………………. 63
4.2. Synthesis of Cholesterol …………………………. 63
4.3. Conversion of Cholesterol to Bile Acids ……………… 66
4.4. Abnormalities of Cholesterol Metabolism …………….. 69
4.4.1. Wolman’s Disease ……………………….. 69
4.4.2. Cholesterol Ester Storage Disease……………………….. 70
4.4.3. Cerebrotendinous Xanthomatosis …………….. 70
4.4.4. ~-Sitosterolemia with Xanthomatosis ………….. 71
4.4.5. Pseudohomozygous Familial Hypercholesterolemia………………………71
4.4.6. Familial LCAT Deficiency …………………. 71
4.5. Cholelithiasis (Gallstones) ………………………… 72
References …………………………………… 73
Chapter 5
Disorders of Lipoprotein Metabolism: Dyslipoproteinemias 75
5.1. Plasma Lipoproteins and Apoproteins: General Aspects ……………………… 75
5.2. Structure and Function of Apoproteins ……………….. 79
5.2.1. ApoA-I ……………………………….. 82
5.2.2. ApoA-ll ………………………………. 82
5.2.3. ApoA-IV ………………………………. 83
5.2.4. ApoB-100 and ApoB-48 …………………… 83
5.2.5. ApoC-I ……………………………….. 84
5.2.6. ApoC-ll ………………………………………..84
5.2.7. ApoC-ill ………………………………. 84
5.2.8. ApoE …………………………………………..85
5.3. Metabolism of Lipoproteins …………………………………….89
5.3.1. Lipoprotein Lipase…………………………………..89
5.3.2. Hepatic Lipase ………………………….. 90
5.3.3. Metabolism of Chylomicrons ……………….. 90
5.3.4. Metabolism of Very-Low-Density Lipoproteins……………………..92
5.3.5. Metabolism of High-Density Lipoproteins ………. 94
5.4. LDL, LDL Receptor, and HMGR ………………….. 98
5.4.1. Metabolism of LDL ………………………. 98
5.4.2. Structure of LDL and the LDL Receptor………………………….100
5.4.3. Variant of the LDL ………………………. 102
5.4.4. Synthesis of the LDL Receptor……………………………………103
5.4.5. The LDL Receptor mRNA and Gene …………………………….104
5.4.6. Mutations of the LDL Receptor ……………… 104
5.4.7. Structure of HMGR ………………………. 105
5.4.8. Synthesis of HMGR………………………………………..105
5.4.9. HMGR mRNA and Gene ………………….. 105
5.4.10. Coordinate Regulation of HMGR and the
LDL Receptor ………………………………………………. 107
5.5. Pathogenesis of Hyperlipoproteinemias ………………. 107
5.6. Factors Leading to Hyperlipidemias …………………. 109
5.7. Mechanisms of Hyperlipidemias ……………………. 109
5.7.1. Defects in Lipoprotein Lipase and ApoC-ll ……… 109
5.7.2. Defects in LDL Clearance………………….. 110
5.7.3. Defects in ApoE and in Remnant Removal ……… 111
5.8. Lipoprotein Metabolism in Diabetes …………………. 113
5.9. Hypolipoproteinemias …………………………… 115
5.9.1. HDL Deficiency (Tangiers Disease) …………… 115
5.9.2. LCAT Deficiency……………………………………………..115
References …………………………………… 115
Chapter 6
Cholesterol, Lipoproteins, and Atherosclerosis 121
6.1. Atherosclerosis ………………………………… 121

6.1.1. Early History of Atherosclerosis ………………123
6.1.2. Experimental Atherosclerosis ………………..123
6.1.3. Epidemiological Data ………………………124
6.2. Survey Studies: Cholesterol and CHD ………………..124
6.3. Alcohol Intake and CHD ………………………….127
6.4. Drug Therapy for Hyperlipidemias …………………..129
6.5. Postulated Mechanisms of Atherosclerosis ……………..129
References…………….132
Chapter 7
Dietary Management of Elevated Blood Lipids

7.1. Dietary Lipids, Hyperlipidemia, and Heart Disease ……… 135
7.1.1. Dietary Lipids ……………………………………………..137
7.1.2. Effects of Dietary Fatty Acids on Plasma Lipids and
Lipoproteins ……………………………. 139
7.1.3. Effects of Dietary Fatty Acids on Platelet
Aggregation ……………………………. 141
7.1.4. Role of Dietary 00-3 Fatty Acids in Heart Disease…. 141
7.1.5. Conversion of Polyunsaturated Fatty Acids
to Prostaglandins ………………………… 142
7.1.6. Relation of Dietary Lipids to CHD …………………………………. 146
7.1.7. Influence of Egg Consumption on Blood Cholesterol. . 147
7.1. 8. Exercise and Heart Disease …………………. 150
7.1.9. Fad Diets and Other Dietary Agents………………………..150
7.1.10. Excessive Vitamin Intake ………………….. 151
7.2. Biochemical Effects of Polyunsaturated Fatty Acids ……………………………..152
7.2.1. Types of Polyunsaturated Fatty Acids …………. 153
7.2.2. 00-6 Fatty Acids and Plasma Lipids …………… 154
7.2.3. Membrane Fatty Acid Composition and
Lipoprotein Metabolism …………………………………………156
7.2.4. 00-3 Fatty Acids and Plasma Lipids …………………………..156
7.2.5. Hypolipidemic Mechanisms of the 00-3
Fatty Acids …………………………….. 158
7.3. Platelet and Blood Vessel Prostaglandins Derived from Dietary
Polyunsaturated Fatty Acids ………………………. 159
7.4. Effects of Polyunsaturated Fatty Acids on Platelet Function… 160
7.4.1. Linoleic Acid…………………………… 160
7.4.2. Linolenic Acid ………………………….. 161
7.4.3. Eicosapentenoic Acid… . … .. .. …. .. . . …. .. . . 161
7.5. Platelet Lipid Composition ……………………….. 161
7.6. Platelet and Vascular Function …………………….. 162
7.7. Mechanisms of Fatty Acid Effects ………………….. 162
7.8. Possible Risks and Side Effects from Increased Amounts of
Dietary Polyunsaturated Fatty Acids………………………………….. 163
7.8.1. 00-6 Fatty Acids …………………………. 163
7.8.2. 00-3 Fatty Acids …………………………. 164
References …………………………………… 166
Chapter 8
Drug Therapy for Hyperlipidemias: Lipid-Lowering Drugs and
Antithrombic and Fibrinolytic Drugs ……………………………169
8.1. Lipid-Lowering Drugs …………………………… 169
8.2. Combined Drug Therapy ………………………………. 172
8.3. Antithrombic Drugs …………………………….. 174
8.3.1. Endothelial Injury ………………………… 174
8.3.2. Platelet Adherence and Aggregation……………………. 175
8.3.3. Thrombin and Fibrin Formation ……………… 176
8.3.4. Plasmin Formation and Fibrinolysis …………… 177
8.4. Fibrinolytic Drugs ……………………………… 178
8.5. Mechanisms of Action of Antithrombic Drugs …………. 179
8.6. Arachidonic Acid Release Inhibitors………………………………… 181
8.7. Drugs That Inhibit cAMP Formation in Platelets …………………….. 182
8.8. Membrane-Active Drugs …………………………. 182
8.9. Anticoagulants and Other Drugs ……………………. 182
8.10. Antithrombic Drugs for Treatment of CHD ……………. 183
8.10.1. Anticoagulant Therapy for MI ……………………………184
8.10.2. Long-Term Anticoagulant Therapy for MI ……………………………..184
8.10.3. Platelet Inhibitors and Acute MI ……………… 185
References …………………………………… 185
Chapter 9
Lung Surfactant Deficiency: Respiratory Distress Syndrome of
the Newborn…………………………………… 189
9.1. Early History …………………………………. 189
9.2. Properties of DPPC …………………………….. 192
9.3. Lung Surfactant ……………………………….. 193
9.4. Synthesis of Lung Surfactant Phospholipids…………………………… 196
9.5. Hormonal Regulation of the Synthesis of Lung Surfactant. . . . ………………..200
9.6. Therapy for RDS ………………………………. 202
References …………………………………… 203
Chapter 10
Sphingolipidoses: Gangliosidoses, Tay-Sachs Disease, and
Sandhoff’s Disease …………………………………. 205
10.1. Early History …………………………………. 205
10.2. Genetic Defects ……………………………….. 205
10.3. Sphingolipids …………………………………. 207
10.3.1. Biosynthesis of the Spbingolipids …………….. 207
10.3.2. Enzymatic Degradation of the Gangliosides ………………………………… 209
10.3.3. Distribution of Gangliosides in the Brain…………………………… 209
10.3.4. Types and Clinical Features of GM2 Gangliosidoses……………………210
10.4. Overview of the Sphingolipidoses…………………. 211
10.5. Therapeutic Approaches for the Sphingolipidoses ……….. 214
References …………………………………… 214
Index ……………………………………………. 215

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