Carbohydrate Metabolism and Biological Oxidation Table of Contents
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Carbohydrate Metabolism and Biological Oxidation Table of Contents 1. Digestion and Absorption of Carbohydrates 2. Hormonal Control of Carbohydrate Metabolism 3.Glycogen Synthesis and Degradation 24.4 Gluconeogenesis 24.5 The Pentose Phosphate Pathway 24.6 Glycolysis 24.7 Terminology for Glucose Metabolic Pathways 24.8 The Citric Acid Cycle 24.9 The Electron Transport Chain 24.10 Oxidative Phosphorylation 11. ATP Production for the Complete Oxidation of Glucose 12. Importance of ATP 13. Non-ETC Oxygen-Consuming Reactions 14. B-Vitamins and Carbohydrate Metabolism Copyright © Cengage Learning. All rights reserved 2 Digestion and Absorption of Carbohydrates Copyright © Cengage Learning. All rights reserved 3 Digestion and Absorption of Carbohydrates • Carbohydrate digestion: Begins in the mouth – Salivary enzyme “α-amylase” catalyzes the hydrolysis of α- glycosidic linkages of starch and glycogen to produce smaller polysaccharides and disaccharide – maltose – Only a small amount of carbohydrate digestion occurs in the mouth because food is swallowed so quickly into the stomach • In stomach very little carbohydrate is digested: – No carbohydrate digestion enzymes present in stomach – Salivary amylase gets inactivated because of stomach acidity Copyright © Cengage Learning. All rights reserved 4 Digestion and Absorption of Carbohydrates • The primary site for the carbohydrate digestion is within the small intestine – Pancreatic α-amylase breaks down polysaccharide chains into disaccharide – maltose • The final step in carbohydrate digestion occurs on the outer membranes of intestinal mucosal cells – Maltase – hydrolyses maltose to glucose – Sucrase – hydrolyses sucrose to glucose and fructose – Lactase – hydrolyses lactose to glucose and galactose • Glucose, galactose, and fructose are absorbed into the bloodstream through the intestinal wall. • Galactose and Fructose are converted to products of glucose metabolism in the liver. Copyright © Cengage Learning. All rights reserved 5 Section 24.1 Digestion and Absorption of Carbohydrates • Following absorption the monosaccharides are carried by the portal vein to the liver where galactose and fructose are enzymatically converted to glucose intermediates that enter into the glycolysis pathway • The glucose may then pass into the general circulatory system to be transported to the tissues or converted to glycogen reserve in the liver. • The glucose in the tissues may be a) oxidized to CO2 and H2O (ATP) b) converted to fat c) converted to muscle glycogen Copyright © Cengage Learning. All rights reserved 6 Metabolism • Blood-sugar level: – the proper functions of the body are dependent on precise control of the glucose concentration in the blood. – the normal fasting level of glucose in the blood is 70-90 mg/100 ml. • Abnormal conditions: • A. hypoglycemia – condition resulting from a lower than the normal blood-sugar level (below 70 mg/100 ml) – extreme hypoglycemia, usually due to the presence of excessive amounts of insulin, is characterized by general weakness, trembling, drowsiness, headache, profuse perspiration, rapid heart beat, lowered blood pressure and possible loss ofconsciousness. – Loss of consciousness is most likely due to the lack of glucose in the brain tissue, which is dependent upon this sugar for its energy. • B. hyperglycemia – higher than the normal level (above 120 mg/100 mL); when the pancreas does notsecrete enough insulin – may temporarily exist as a result of eating a meal rich in carbohydrates. – extreme hyperglycemia, the renal threshold (160-170 mg/100 mL) is reached and excess glucose is excreted in the urine Copyright © Cengage Learning. All rights reserved 7 Hormonal Control of Carbohydrate Metabolism • Besides enzyme inhibition, carbohydrate metabolism may be regulated by hormones • Three major hormones control carbohydrate metabolism: – Insulin ; Glucagon ; Epinephrine • Insulin • 51 amino acid polypeptide secreted by the pancreas • Promotes utilization of glucose by cells • The release of insulin is triggered by high blood-glucose levels • Its function is to lower blood glucose levels by enhancing the formation of glycogen from glucose (glycogen synthesis) • The mechanism for insulin action involves insulin binding to proteins receptors on the outer surfaces of cells which facilitates entry of the glucose into the cells Copyright © Cengage Learning. All rights reserved 8 Hormonal Control of Carbohydrate Metabolism Glucagon • 29 amino acid peptide hormone produced in the pancreas • Released when blood glucose levels are low • Principal function is to increase blood-glucose concentration by speeding up the conversion of glycogen to glucose (glycogenolysis) in the liver • Glucagon elicits the opposite effects of insulin Epinephrine (also called adrenaline) • Released by the adrenal glands in response to anger, fear, orexcitement • Function is similar to glucagon, i.e., stimulates glycogenolysis • Primary target of epinephrine is muscle cells • Promotes energy generation for quick action Copyright © Cengage Learning. All rights reserved 9 Metabolism • There are six major metabolic pathways of glucose: 1) Glycogenesis 2) Glycogenolysis 3) Gluconeogenesis 4) Hexose monophosphate shunt 5) Glycolysis 6) Citric Acid Cycle Copyright © Cengage Learning. All rights reserved 10 Glycogen Synthesis and Degradation Glycogenesis and Glycogenolysis • Involved in the regulation of blood glucose concentration • When the dietary intake of glucose exceeds immediate needs, humans and other animals can convert the excess to glycogen, which is stored in either the liver or muscle tissue. • Glycogenesis is the pathway that converts glucose into glycogen. • When there’s need for additional blood glucose, glycogen is hydrolyzed and released into the bloodstream. • Glycogenolysis is the pathway that hydrolyzes glycogen to glucose. Copyright © Cengage Learning. All rights reserved 11 Gluconeogenesis • Metabolic pathway by which glucose is synthesized from non- carbohydrate sources: – The process is not exact opposite of glycolysis • Glycogen stores in muscle and liver tissue are depleted with in 12-18 hours from fasting or in even less time from heavy work or strenuous physical activity • Without gluconeogenesis, the brain, which is dependent on glucose as a fuel would have problems functioning if food intake were restricted for even one day • Gluconeogenesis helps to maintain normal blood-glucose levels in times of inadequate dietary carbohydrate intake • About 90% of gluconeogenesis takes place in the liver • Non-carbohydrate starting materials for gluconeogenesis: – Pyruvate – Lactate (from muscles and from red blood cells) – Glycerol (from triacylglycerol hydrolysis) – Certain amino acids (from dietary protein hydrolysis or from muscle protein during starvation) Copyright © Cengage Learning. All rights reserved 12 The Pentose Phosphate Pathway Hexose monophosphate shunt • Initial reactant of the pathway is glucose-6- phosphate • Also termed phosphogluconate pathway, because 6–phosphogluconate is one of the intermediates • A third name is pentose phosphate pathway, because ribose-5-phosphate is one of its products • The main purposes of the HMP shunt are the following: – to produce ribose-5-P for nucleotide synthesis – to produce NADPH from NADP+ for fatty acid and steroid biosynthesis and for maintaining reduced glutathione (GSH) inside erythrocytes – to interconvert pentoses and hexoses Copyright © Cengage Learning. All rights reserved 13 Glycolysis • A series of reactions in the cytoplasm which converts glucose (C6) to two molecules of pyruvate (a C3 carboxylate), and ATP and NADH are produced. • Also called Embden-Meyerhof pathway, after the scientist who elucidated the pathway • an anaerobic process; each step takes place without O2; one of its advantages, the body can obtain energy from glycolysis quickly, without waiting for a supply of O2 to be carried to the cells. • occurs in cells lacking mitochondria, e.g., erythrocytes and in certain skeletal muscle cells during intense muscle activity Copyright © Cengage Learning. All rights reserved 14 Glycolysis • Step 1: Formation of glucose-6-phosphate: – Endothermic reaction catalyzed by hexokinase – Energy needed is derived from ATP hydrolysis • Step 2: Formation of Fructose-6-phosphate: – Enzyme: Phosphoglucoisomerase • Step 3: Formation of Fructose 1,6-bisphosphate: – Enzyme: phosphofructokinase • Step 4: Formation of Triose Phosphates: – C6 species is split into two C3 species – Enzyme : Aldolase • Step 5: Isomerization of Triose Phosphates – DHAP is isomerized to glyceraldehyde 3- phosphate – Enzyme: Triosephosphate isomerase • Step 6: Formation of 1,3-bisphosphoglycerate – Glyceraldehyde 3-phosphate is oxidized and phosphorylated – Enzyme: Glyceraldehyde-3-phosphate dehydrogenase Copyright © Cengage Learning. All rights reserved 15 Glycolysis • Step 7: Formation of 3-bisphosphoglycerate – It is an ATP producing step – Enzyme: phosphoglycerokinase • Step 8: Formation of 2-phosphoglycerate – Isomerization of 3-phosphoglycerate to 2-phosphoglycerate – Enzyme: phosphoglyceromutase • Step 9: Formation of Phosphoenolpyruvate: – Enzyme: Enolase • Step 10: Formation of Pyruvate: – High energy phosphate is transferred from phosphoenolpyruvate to ADP molecule to produce ATP and pyruvate – Enzyme: Pyruvate kinase • At this point of carbohydrate metabolism there are at least 2 directions that the product pyruvate may take. • The direction depends primarily upon the availability of oxygen in the cell: Copyright © Cengage Learning.