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Chapter-09 Major Metabolic Pathways of Glucose

BOOK TITLE: Textbook of Biochemistry for Medical Students

Author
1. Vasudevan DM
2. S Sreekumari
3. Vaidyanathan Kannan
ISBN
9789350250167
DOI
10.5005/jp/books/11359_9
Edition
6/e
Publishing Year
2011
Pages
23
Author Affiliations
1. Faculty of Medicine, Amrita Vishwa Vidyapeetham, (Amrita University), Kochi, Kerala, Formerly Principal, College of Medicine, Amrita, Kerala; Formerly, Dean, Sikkim Manipal Institute of Medical Sciences, Gangtok, Sikkim, Amrita Vishwa Vidyapeetham (Deemed University), Cochin, Kerala, E-mail: dmvasudevan@aims.amrita.edu, PG Programs and Research College of Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India, College of Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India; Sikkim Manipal Institute of Medical Sciences, Gangtok, Sikkim, India
2. Jubilee Mission Medical College, Trissur, Kerala, Sree Gokulam Medical College and Research Foundation, Thiruvananthapuram, Kerala, India, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India, Government Medical College, Thrissur and Thiruvananthapuram, Kerala, India; Sree Gokulam Medical College and Research Foundation, Thiruvananthapuram, Kerala, India; Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
3. Amrita Institute of Medical Sciences, Kochi, Kerala, India, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India, Believers Church Medical College and Hospital, Thiruvalla, Kerala, India
Chapter keywords

Abstract

Digestion of carbohydrates occurs at the mouth by salivary amylase and in the intestine by pancreatic amylase and specific enzymes such as sucrase, maltase, lactase, etc. Deficiency of Lactase results in lactose intolerance. Special Glucose transporters; GluT1, GluT2, GluT3, GluT4, GluT5 and GluT7 perform the function of absorption of glucose in various cells, tissues and organs of the body. The GluT4 has been implicated in Type 2 diabetes mellitus. Glycolysis occurs both in aerobic and anaerobic conditions. Anaerobic glycolysis is the major source of energy for muscles, when the muscle tissue lacks oxygen. Irreversibility of the hexokinase reaction can be circumvented by glucose-6-phosphatase, which is a key enzyme of gluconeogenesis. Phosphofructokinase (PFK) is the regulatory or rate limiting enzyme of glycolysis. It is an allosteric and inducible enzyme. AMP is allosteric activator, while citrate and ATP are allosteric inhibitors. The reaction catalyzed by 1, 3-bisphospho glycerate kinase and pyruvate kinase are examples of substrate level phosphorylation. Energy generating steps of glycolysis are catalyzed by the enzymes glyceraldehyde-3-phosphate dehydrogenase; 1, 3-bisphosphoglycerate kinase and pyruvate kinase. Cori’s cycle ensures efficient reutilization of lactate produced in the muscle. Under anaerobic conditions, glycolysis is inhibited by oxygen. This effect is called Pasteur Effect. Total energy yield from glycolysis is 7 ATP. Total net ATP generation from one glucose molecule is 32. Under anaerobic condition pyruvate is reduced to lactate by lactate dehydrogenase. Under aerobic conditions, it is oxidatively decarboxylated to acetyl CoA by the enzyme complex Pyruvate dehydrogenase (PDH). The components of PDH complex are; pyruvate decarboxylase, dihydrolipoyl transacetylase and dihydrolipoyl dehydrogenase. The PDH enzyme complex requires 5 cofactors for its activity viz. NAD, FAD, TPP, Lipoamide and Co A. The PDH reaction is a totally irreversible reaction. Hence, there is no net synthesis of glucose from fat. Key enzymes of gluconeogenesis are: pyruvate carboxylase, phosphoenol pyruvate carboxykinase, fructose-1, 6-bisphosphatase and glucose-6-phosphatase. Major substrates for gluconeogenesis are lactate and glucogenic amino acids. Glycogen is the storage polysaccharide of the body. It is stored mainly in the liver and muscle. The enzymes glycogen phosphorylase and glycogen synthase are regulated by covalent modification. Glycogen phosphorylase is activated by glucagon and adrenaline, while glycogen synthase is activated by insulin. Glycogen storage diseases (GSD) are in born errors of metabolism. Type 1 is called von Gierke\'s disease.

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