lecnote fm Med Biochem - Carter Center

1 LECTURE NOTES. For Health Science Students Medical Biochemistry Solomon Adugna, Lakshmi Ahuja Mekonnen Alemu, Tsehayneh Kelemu, Henok Tekola, Belayhun Kibret, Solomon Genet Gondar University, Jimma University, Debub University In collaboration with the Ethiopia Public Health Training Initiative, The Carter Center , the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education 2004. Funded under USAID Cooperative Agreement No. 663-A-00-00-0358-00. Produced in collaboration with the Ethiopia Public Health Training Initiative, The Carter Center , the Ethiopia Ministry of Health, and the Ethiopia Ministry of Education. Important Guidelines for Printing and Photocopying Limited permission is granted free of charge to print or photocopy all pages of this publication for educational, not-for-profit use by health care workers, students or faculty. All copies must retain all author credits and copyright notices included in the original document.

2 Under no circumstances is it permissible to sell or distribute on a commercial basis, or to claim authorship of, copies of material reproduced from this publication. 2004 by Solomon Adugna, Lakshmi Ahuja Mekonnen Alemu, Tsehayneh Kelemu, Henok Tekola, Belayhun Kibret, Solomon Genet All rights reserved. Except as expressly provided above, no part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written permission of the author or authors. This material is intended for educational use only by practicing health care workers or students and faculty in a health care field. Table of Contents Table of i v Introduction .. vi Solomon Adugna and Lakshmi Ahuja Unit One: Enzymes .. 1. Henok Tekola Principles and classifications of Enzymes .. 5. Mechanism action of Enzymes .. 7. Enzyme Inhibition.

3 13. Regulation of Enzyme activity .. 18. Enzymes in clinical diagnosis .. 19. Unit Two: Carbohydrate Metabolism .. 23. Belayhun Kibret Chemistry of Carbohydrates .. 23. Functions of Carbohydrates .. 31. Digestion and absorption of Carbohydrates .. 33. Glycolysis .. 35. Glycogen Metabolism .. 42. Glycogen storage diseases .. 45. Pentose phosphate pathway .. 46. The Cori - cycle .. 48. Gluconeogenesis .. 49. Unit Three: Integrative Metabolism Bioenergetics .. 54. Tsehayneh Kelemu Introduction .. 54. Structural basis of high energy phosphate .. 55. Formation and utilization of ATP .. 56. Catabolism of fuel molecules .. 56. Concept of Free energy .. 58. Oxidation-reduction reactions .. 58. Aerobic energy generation .. 61. Kreb's cycle .. 63. Function and regulation of kreb's cycle .. 70. i Electron transport system and oxidative Phosphorylation .. 71. Respiratory control .. 77. Uncouplers .. 77. Respiratory poisons .. 78.

4 Unit Four: Lipid Metabolism .. 80. Solomon Genet Classification of Lipids .. 80. Types of Lipids .. 80. Digestion and absorption of Lipids .. 86. Metabolism of Fatty acids and Triacyl Glycerols .. 88. -Oxidation of Fatty acids .. 90. Metabolism of Ketone bodies .. 93. Biosynthesis of Fatty acids and triacyl glycerols .. 97. Cholesterol Metabolism .. 99. Atherosclerosis .. 101. Hypercholesterolemic drugs .. 101. Lipid storage diseases .. 102. Fatty Liver .. 102. Lipoproteins .. 102. Chemical compositions of Membranes .. 104. Unit Five: Amino acids and Proteins .. 105. Solomon Adugna Classification of amino acids .. 106. Properties of amino acids .. 115. Peptides .. 119. Glutathione synthesis .. 121. Proteins .. 124. Classifications of proteins .. 124. Levels of organization of proteins .. 126. Denaturation of proteins .. 131. Hemoglobin and Myoglobin .. 135. Sickle cell Hemoglobin .. 136. Sickle cell disease, Sickle cell 136.

5 Digestion and absorption of proteins .. 137. Amino acid catabolism .. 141. Nitrogen balance, excretion and the urea 144. ii Defects in the urea cycle .. 150. The Glucose - Alanine cycle .. 151. Inborn errors of amino acid 152. Amino acid derived nitrogenous compounds .. 154. Clinical problems .. 159. Unit Six: Vitamins and Coenzymes .. 161. Solomon Adugna Water soluble vitamins .. 161. Chemistry, sources, function and deficiency of: Thamine .. 161. Riboflavin .. 163. Niacin .. 164. Pyridoxine .. 165. Biotin .. 166. Cobalamin .. 167. Folic acid .. 169. Panthothenic .. 170. Ascorbic acid .. 171. Fat soluble vitamins .. 172. Chemistry, Sources, function, deficiency and Hypervitaminosis of: Vitamin A .. 173. Vitamin D .. 177. Vitamin E .. 179. Vitamin K .. 181. Unit Seven: Miniral Metabolism .. 183. Lakshmi Ahuja Mineral .. 183. Sodium and potassium .. 183. Calcium and Phosphate .. 184. Trace elements .. 185. Iron .. 185. Copper.

6 187.. 188. Flourine .. 188. Iodine .. 189. Zinc .. 189. iii Selenium .. 191. Unit Eight: Hormones .. 193. Lakshmi Ahuja Definition and classification .. 194. Biosynthesis, storage, transport .. 196. Mechanism of action of steroid hormones .. 197. Mechanism of action of protein hormones .. 198. Receptors and diseases .. 202. Second messengers .. 203. Insulin synthesis, secretion and metabolic role .. 205. Diabetes mellitus .. 209. Symptoms and complications of DM.. 210. Glucagon .. 211. Clinical .. 212. Thyroxin .. 213. Synthesis and Metabolism .. 213. Hypo and Hyper Thyroidism .. 214. Goiter .. 215. Catecholamines .. 216.. 217. Case Histories .. 217. Unit Nine: Molecular Genetics .. 220. Mekonnen Alemu Structure of Nucleic acids .. 220. Types of Nucleic acids .. 226. Replication of DNA .. 230. DNA Damage and repair mechanism .. 231. RNA synthesis .. 233. Post transcriptional Modifications .. 236. Translation/Protein synthesis.

7 240. Regulation of protein synthesis .. 242. The Genetic code .. 243. Post translational processes .. 244. Glossary .. 246. Reference .. 253. iv ACKNOWLEDGMENT. The team of authors from the department of Biochemistry of various Universities would like to thank and express their deep rooted gratitude to the Carter Center (EPHTI) for its initiation and drive to prepare this teaching material. The Center has not only supported the team financially, but also stood behind it firmly throughout the entire period of this experience. Thus Carter Center has become the pioneer in the field of preparing teaching material and also in training a team of authors for future endeavors of the kind. In addition, the task would have been impossible without the directing of the Federal Democratic Republic of Ethiopia, Ministry of Education. It is also not out of place to thank the administration of Gondar University, Debub University and Jimma University for extending cooperation whenever it was needed.

8 The authors extend their appreciation to Ato Akililu Mulugeta, Manager, Carter Center , who has shepherded the team's effort through manuscript to finished pages. The authors are particularly grateful to Abdel-Aziz Fatouh Mohammed ( ) Associate professor of Biochemistry, Medical Faculty, Addis Ababa University and Ato. Daniel Seifu, Lecturer of Medical Biochemistry, Medical Faculty, Addis Ababa University for their highly professional editing and most helpful comments about many aspects of the text. v INTRODUCTION TO BIOCHEMISTRY. Medical biochemistry is an essential component of curriculum for all categories of health professionals. Contemporary Biochemistry plays a crucial role in the Medical field, be it metabolic pathways, storage diseases, mechanism action of varied biomolecules or inter and intra cellular communications. A lecture note on Medical biochemistry integrates and summarizes the essentials of the core subject.

9 Topics are carefully selected to cover the essential areas of the subject for graduate level of Health sciences. The chapters are organized around the following major themes: 1. Conformation of biomolecules, structure and their relationship to biological activity 2. synthesis and degradation of major metabolites 3. Production and storage of energy 4. Biocatalysts and their application 5. Intercellular communication by hormones 6. Molecular events in gene expression and regulation Enzymes: Body proteins perform a large number of functions. One such unique function is, they act as biological catalysts (Enzymes) .They are responsible for highly complex reactions. They direct the metabolic events and exhibit specificity toward substrates, regulate the entire metabolism. Thus, they play key role in the degradation and synthesis of nutrients, biomolecules etc. The most important diagnostic procedures involves assay of enzymes.

10 They assist to know damaged tissues, the extent of tissue damage, helps to monitor the course of the disease and used as a therapeutic means of diagnosing a vast array of diseases. Amino acids and Proteins Living systems are made up of Proteins .They are the dehydration polymers of amino acids. Each amino acid residue is joined by a peptide linkage to form proteins. Proteins are the molecular instruments in which genetic information is expressed, Hormones, Antibodies, transporters, the lens protein, the architectural framework of our tissues and a myriad of substances having distinct biological activities are derived. The type, nature and number of amino acids impart characteristic properties to the proteins. There are about 300 amino acids, but only 20 are coded by DNA of higher organisms. acid base properties of amino acids are important to the individual physical and chemical nature of vi the protein. The structural organization of proteins could be primary, secondary, tertiary and quaternary.