كاربوهايدرات - عملية التمثيل الغذائي PDF

‫ْ‬ ‫ُ‬ ‫َوقل َّرب زدني‬ ‫ْ‬ ‫عل ًما‬ ‫سورة طه ‪ -‬اآلية ‪114‬‬ Carbohydrate Metabolism Directed by Pro.Dr/ Maathir kamel Intended learning outcomes (ILOs): A) Knowledge and Understanding By the end of the course, students should be able to: A1:Describe the digestio...

‫ْ‬ ‫ُ‬ ‫َوقل َّرب زدني‬ ‫ْ‬ ‫عل ًما‬ ‫سورة طه ‪ -‬اآلية ‪114‬‬ Carbohydrate Metabolism Directed by Pro.Dr/ Maathir kamel Intended learning outcomes (ILOs): A) Knowledge and Understanding By the end of the course, students should be able to: A1:Describe the digestion of carbohydrates and its disorders A2:Describe absorption of carbohydrates A3: Define metabolism, A4:Describe the pathway of glycolysis and its control, and explain how glycolysis can operate under anaerobic conditions and its role in energy production.. INTRODUCTION  Metabolism Metabolism means the fate of food molecules after digestion and absorption. Metabolic pathways include the following A-Anabolic pathways: Involved in the synthesis of the compounds constituting the structure of the body e.g. protein synthesis. These pathways require free energy (comes from the catabolic pathways). B-Catabolic pathways: These involve the breakdown (catabolic) reactions to which the compound is subjected. These involve the oxidative processes that release free energy in the form of high energy phosphate or reducing equivalents. Examples include: the respiratory chain and oxidative phosphorylation. C-Amphibolic pathways: These act as links between the catabolic and anabolic pathways e.g. citric acid cycle. Carbohydrates provide 50% of daily calories in our diet. When glucose is completely oxidized to CO2 and H2O the energy change is 4 Kcal/gram. Starches make up approximately 50% of the dietary carbohydrates that can be metabolized. Many foods contain starches e.g. potatoes, grains, and flour products. Some monosaccharides, such as fructose and glucose, are present in fruits and honey.  Disaccharides provide most of the rest of the carbohydrates intake e.g. sucrose and lactose. The polysaccharides and disaccharides cannot be absorbed directly by the intestinal mucosa. Several enzymes are involved in converting starches and disaccharides to monosaccharides, which can be absorbed. Little or no starch or monosaccharide is present in feces.  DIGESTION OF CARBOHYDRATES Carbohydrate digestion begins in the mouth with the aid of salivary amylase, which converts starch and glycogen to dextrins. Further action of the pancreatic amylase completes the digestion of dextrins to maltose. The enzymes maltase, lactase and sucrase hydrolyze the corresponding disaccharides to their constituent monosaccharides e.g. glucose, fructose and galactose,which can be absorbed. The absorbed glucose takes part in many processes: Release of energy by oxidation of glucose in the tissues, producing CO2 and H2O. This energy can be stored as ATP. Synthesis of other carbohydrates e.g. pentoses, galactose and lactose. Conversion to its storage form, glycogen, by the process of glycogenesis occurring in the skeletal muscle and liver. Glucose intermediates provide the carbon skeleton of non-essential amino acids e.g. intermediates of the citric acid cycle. Synthesis of long-chain fatty acids (lipogenesis) and cholesterol from Acetyl-CoA (derived from pyruvate). METABOLIC PATHWAYS OF CARBOHYDRATES After absorption of monosaccharides, the only sugar circulates in blood is glucose, which pass into two main pathways: A-Catabolic pathways: involving oxidative pathways and include: 1. Glycolysis: by which glycogen or glucose is oxidized to pyruvic or lactic acid. 2. Citric acid cycle: by which acetyl CoA derived from pyruvate is completely oxidized to CO2 and H2O. 3. Glycogenolysis: is the breakdown of glycogen to glucose. 4. Hexose monophosphate shunt: by which oxidation of glucose produces pentoses and reducing equivalents. 5. Uronic acid pathway: by which glucose gives glucuronic acid and pentoses. B-Anabolic pathways: these include: 1. Gluconeogenesis: by which glucose is synthesized from non-carbohydrate sources e.g. glycerol, lactic acid, propionic acid and amino acids. 2. Glycogenesis: by which glycogen is synthesized from glucose. GLYCOLYSIS  Glycolysis is the major pathway for the oxidation of glucose. Importance of glycolysis: 1. Glycolysis provides the main pathway for the metabolism of fructose and galactose derived from the diet. 2. It has the ability to provide ATP in the absence of oxygen. This allows skeletal muscle to perform at very high levels during muscular contraction. 3. Deficiency of enzymes of glycolysis causes a number of diseases, which are mainly manifested as hemolytic anemia and fatigue.  Intracellular site: Cytosol of the cell. Steps: Glycolysis can be separated into aerobic and anaerobic phases. The reactions are the same in the presence of oxygen as in its absence, except in the extent and end products. Figure (1) showing steps of glycolysis  *Conversion of glucose to glucose 6 phosphate by glucokinase or hexokinase Glucokinase Hexokinase 1-It is present in liver cells only. - Present in all cells except liver cells 2-It has low affinity (high Km) - Has high affinity (low Km) for glucose. for glucose. 3. It is specific for glucose. - It catalyzes phosphorylation of other hexoses but at much slower rate than glucose. 4-Its function is to remove - Its function is to supply glucose to the glucose from the blood tissues even in the presence of low following a meal. blood glucose concentration. - No effect. 5-Insulin induces its synthesis. - Allosterically inhibited by G-6-p. 6-G-6-p has no effect on it. *At the end, Pyruvate proceeds via one of 2 pathways, depending on the presence or absence of oxygen as follows: a) In presence of oxygen, pyruvate is oxidized in the citric acid cycle after conversion to acetyl-COA. b) In the absence of oxygen as in erythrocytes and skeletal muscle during exercise, pyruvate is reduced to lactate, catalyzed by the enzyme lactate dehydrogenase, which utilizes NADH+H+ that is produced in reaction (5). The reoxidation of NADH+H+ by this reaction provides NAD which allows glycolysis to proceed in the absence of oxygen. Energy generated from glycolysis ATP produced: 1. The reaction catalyzed by glyceraldhyde-3-phosphate dehydrogenase generates 6 ATP from the oxidation of 2 NADH in the respiratory chain (in the presence of oxygen). 2. The reaction catalyzed by phosphoglycerate kinase generates 2 ATP (at substrate level). 3. The reaction catalyzed by pyruvate kinase generates 2ATP (at substrate level). So the total = 6 +2+2= 10ATP in the presence of oxygen and 4 ATP in its absence. ATP lost: 2 molecules of ATP are lost by the reactions catalyzed by hexokinase and phosphofructokinase enzymes. So, glycolysis produces 10-2= 8ATP in the presence of oxygen and 4-2=2 ATP in its absence. Inhibitors of Glycolysis: 1- Iodoacetate and Iodoacetic acid: inhibit glyceraldehyde-3 phosphate dehydrogenase. 2- Arsenite: competes with Pi for glyceraldehyde-3 phosphate dehydrogenase forming 1 arseno 3 phosphoglycerate. 3- Fluoride: inhibits enolase. Sodium fluoride is used to inhibit in vitro glycolysis. Regulation of glycolysis Most of the reactions of glycolysis are reversible, except 3 reactions, which are irreversible. These irreversible reactions are catalyzed by hexokinase, phosphofructokinase and pyruvate kinase. The hexokinase enzyme is Allosterically inhibited by the glucose –6- phosphate. The enzymes involved in the utilization of glucose (i.e. of glycolysis) become more active when there is high blood glucose concentration. This is due to increased synthesis of the key enzymes in glycolysis by insulin which is responsive to blood glucose concentration. The enzyme pyruvate kinase is regulated by covalent modification. It is inactivated by phosphorylation. The enzyme phosphofructokinase-1 is subjected to allosteric modification. It is inhibited by citrate and by ATP and activated by AMP.  Difference between aerobic and anaerobic glycolysis Aerobic Anerobic Energy 8 ATP 2 ATP NAD+ In respiratory chain By lactate regeneration formation Availability to Available Not available krebs' End product Pyruvate Lactate