Carbohydrates Metabolism Lecture PDF

CHAPTER 13: Carbohydrates Metabolism (LECTURE)  Lesson Outline Digestion of Carbohydrates Glycolysis Regulation of Glycolysis Fates of Pyruvate Gluconeogenesis Glycogenesis and Glycogenolysis Cori Cycle Blood Sugar Hormonal Control of Carbohydrate Metabolism  Digestion of Ca...

CHAPTER 13: Carbohydrates Metabolism (LECTURE)  Lesson Outline Digestion of Carbohydrates Glycolysis Regulation of Glycolysis Fates of Pyruvate Gluconeogenesis Glycogenesis and Glycogenolysis Cori Cycle Blood Sugar Hormonal Control of Carbohydrate Metabolism  Digestion of Carbohydrates Dietary carbohydrates serve as energy resources Account for 45–55% of daily energy needs in a typical American diet During carbohydrate digestion, di- and polysaccharides are hydrolyzed to monosaccharides polysaccharides + H 2 O ⎯⎯⎯⎯ → glucose digestion sucrose + H 2 O ⎯⎯⎯⎯ → glucose + fructose digestion lactose + H 2 O ⎯⎯⎯⎯ → glucose + galactose digestion maltose + H 2 O ⎯⎯⎯⎯ → glucose digestion  Digestion of Carbohydrates After digestion is completed, glucose, fructose, and galactose are absorbed into the bloodstream through the lining of the small intestine and transported to the liver In the liver, fructose and galactose are converted to glucose or to compounds that are metabolized by the same pathway as glucose polysaccharides + H 2 O ⎯⎯⎯⎯ → glucose digestion sucrose + H 2 O ⎯⎯⎯⎯ → glucose + fructose digestion lactose + H 2 O ⎯⎯⎯⎯ → glucose + galactose digestion maltose + H 2 O ⎯⎯⎯⎯ → glucosedigestion  Glycolysis Glucose (C6) is catabolically oxidized through a series of steps to pyruvate (C3) Occurs in the cellular cytoplasm Net reaction glucose + 2Pi + 2ADP + 2NAD + → 2Pyruvate + 2ATP + 2NADH + 4H + + 2H 2O In addition to two molecules of pyruvate, two molecules of ATP, two molecules of NADH, four molecules of H+, and two molecules of H2O are produced Glycolysis  Glycolysis Stage 1 A phosphate group is added to glucose in the cell cytoplasm, by the action of enzyme hexokinase. In this, a phosphate group is transferred from ATP to glucose forming glucose,6- phosphate. Stage 2 Glucose-6-phosphate is isomerized into fructose,6-phosphate by the enzyme phosphoglucomutase.  Glycolysis Stage 3 The other ATP molecule transfers a phosphate group to fructose 6- phosphate and converts it into fructose 1,6-bisphosphate by the action of the enzyme phosphofructokinase. Stage 4 The enzyme aldolase converts fructose 1,6-bisphosphate into glyceraldehyde 3- phosphate and dihydroxyacetone phosphate, which are isomers of each other.  Glycolysis Stage 5 Triose-phosphate isomerase converts dihydroxyacetone phosphate into glyceraldehyde 3- phosphate which is the substrate in the successive step of glycolysis. Stage 6 The enzyme glyceraldehyde 3-phosphate dehydrogenase transfers 1 hydrogen molecule from glyceraldehyde phosphate to nicotinamide adenine dinucleotide to form NADH + H+. Glyceraldehyde 3-phosphate dehydrogenase adds a phosphate to the oxidized glyceraldehyde phosphate to form 1,3-bisphosphoglycerate.  Glycolysis Stage 7 Phosphate is transferred from 1,3- bisphosphoglycerate to ADP to form ATP with the help of phosphoglycerokinase. Thus two molecules of phosphoglycerate and ATP are obtained at the end of this reaction. Stage 8 The phosphate of both the phosphoglycerate molecules is relocated from the third to the second carbon to yield two molecules of 2- phosphoglycerate by the enzyme phosphoglucomutase.  Glycolysis Stage 9 The enzyme enolase removes a water molecule from 2-phosphoglycerate to form phosphoenolpyruvate. Stage 10 A phosphate from phosphoenolpyruvate is transferred to ADP to form pyruvate and ATP by the action of pyruvate kinase. Two molecules of pyruvate and ATP are obtained as the end products.  Glycolysis Fructose enters glycolysis as dihydroxyacetone phosphate and glyceraldehyde-3-phosphate Galactose enters glycolysis as glucose-6-phosphate  Glycolysis Regulation of Glycolysis Glycolysis pathway is regulated by hexokinase, phosphofructokinase, and pyruvate kinase Glucose-6-phosphate noncompetitively inhibits hexokinase (feedback inhibition) Phosphofructokinase is inhibited by high concentrations of ATP and citrate Activated by high concentrations of ADP and AMP Pyruvate kinase is inhibited by high concentrations of ATP As glycolysis occurs, the citric acid cycle and electron transport chain produce large quantities of ATP If the ATP level is low, then AMP and ADP levels are high  Glycolysis Regulation of Glycolysis  Fates of Pyruvate After glycolysis, pyruvate can be: Oxidized to acetyl CoA (under aerobic conditions) Reduced to lactate (under anaerobic conditions) Reduced to ethanol (under anaerobic conditions for some prokaryotic organisms) All processes must regenerate NAD+ from NADH so that glycolysis can continue  Fates of Pyruvate Pyruvate Oxidation to Acetyl CoA Occurs in the mitochondria under aerobic conditions Aerobic – in the presence of oxygen Most of the acetyl CoA will be completely oxidized to CO2 in the citric acid cycle NAD+ is regenerated when NADH transfers its electrons to O2 in the electron transport chain Some acetyl CoA will serve as starting material for fatty acid biosynthesis  Fates of Pyruvate Pyruvate Reduction to Lactate Occurs in cells after strenuous or long-term muscle activity because the cellular supply of oxygen is not adequate for the reoxidation of NADH to NAD+ Under anaerobic conditions, animals and some microorganisms can obtain limited energy through lactate fermentation Anaerobic - in the absence of oxygen Lactate fermentation – production of lactate from glucose  Fates of Pyruvate Pyruvate Reduction to Ethanol Under anaerobic conditions, some microorganisms can obtain limited energy through glycolysis Alcoholic fermentation – conversion of glucose to ethanol Overall equation: Step-wise equations: Fates of Pyruvate  Gluconeogenesis Synthesis of glucose from noncarbohydrate molecules ( lactate, certain amino acids, glycerol ) → pyruvate → glucose Primarily occurs in the liver (90%) Helps maintain blood glucose level Occurs in the kidneys, brain, skeletal muscle, or heart in small amounts  Gluconeogenesis Gluconeogenesis originates in the liver or kidney’s cytoplasm or mitochondria. To make oxaloacetate, two pyruvate molecules are required to carboxylate first. This requires one ATP (energy) molecule. NADH converts oxaloacetate to malate, which can then be transported out of the mitochondria. Once malate leaves the mitochondria, it is oxidized back to oxaloacetate. The enzyme Phosphoenolpyruvate carboxykinase (PEPCK) converts oxaloacetate to phosphoenolpyruvate.  Gluconeogenesis By reversing glycolytic processes, phosphoenolpyruvate is converted into fructose 1,6-bisphosphate. Fructose-1, 6-bisphosphate is converted to fructose-6-phosphate in the reaction releasing inorganic phosphate and is catalyzed by fructose- 1,6-bisphosphatase. The enzyme phosphoglucoisomerase converts fructose-6-phosphate to glucose-6-phosphate. Glucose-6-phosphate generates inorganic phosphate that yields free glucose, which enters the blood. Glucose 6-phosphatase is the enzyme involved. Gluconeogenesis  Glycogenesis Synthesis of glycogen from glucose Glucose units bond to a growing glycogen chain Hydrolysis of UTP (uridine triphosphate) provides energy Occurs in all cells but is an especially important function of liver and muscle cells Glycogen is mainly stored in liver and muscle tissue Liver can store 110 g glycogen Muscles can store 245 g glycogen  Glycogenesis Enzyme glycogen synthase forms the new α(1→4) linkages between each glucose unit and lengthens the chain α(1→6) branch points on the chain are inserted by amylose (1,4-1,6)- trans-glycosylase Glycogenesis  Glycogenolysis Breakdown of glycogen to glucose Occurs in the liver, kidney, and intestinal cells but not in the muscle tissue Step 1 - Cleavage of α(1→4) linkages is catalyzed by glycogen phosphorylase (glucose) n + Pi → (glucose) n−1 + glucose -1- phosphate glycogen glycogen with one fewer glucose unit  Glycogenolysis Step 2 - Cleavage of α(1→6) linkages by hydrolysis Hydrolysis is carried out by a debranching enzyme glucose 1-phosphate → glucose 6-phosphate Step 3 - Hydrolysis of glucose 6-phosphate glucose - 6 - phosphate + H 2O → glucose + Pi Glycogenolysis  Glycogenolysis Muscle cells cannot form free glucose from glycogen Can carry out the first two steps of glycogenolysis to produce glucose-6- phosphate for energy production Liver Maintains a relatively constant level of blood glucose Has the capacity to degrade glycogen to glucose, which is released into the blood during muscular activity and between meals Metabolic Pathway of Glucose  Cori Cycle Process in which glucose is converted to lactate in muscle tissue, lactate is reconverted to glucose in liver, and glucose is returned to the muscle During active exercise: Lactate levels increase in muscle tissue and the compound diffuses out of the tissue into the blood Lactate is taken to liver and converted back to pyruvate Pyruvate is converted to glucose by gluconeogenesis pathway and glucose enters the blood and returns to the muscles Cori Cycle Cori Cycle  Blood Sugar Blood sugar level: Amount of glucose present in blood, normally expressed as mg glucose per 100 mL of blood Highest about one hour after a carbohydrate- containing meal Returns to normal after two to two and a half hours Hypoglycemia – lower-than-normal blood sugar level Hyperglycemia – higher-than-normal blood sugar level  Blood Sugar Renal threshold – blood sugar level at which sugar is not completely reabsorbed by the kidneys Glucosuria – condition in which elevated blood sugar levels result in the excretion of glucose in the urine Prolonged hyperglycemia at glucosuric levels is considered serious Liver regulates the blood glucose level Responds to increase in blood glucose after a meal by removing glucose from bloodstream Converts the removed glucose to glycogen or triglycerides Converts glycogen to glucose and synthesizes new glucose from noncarbohydrate substances when blood glucose levels are low  Hormonal Control of Carbohydrate Metabolism Insulin Source - β-cells of pancreas Enhances the absorption of glucose from the blood into cells of active tissue Increases the rate of synthesis of glycogen, fatty acids, and proteins and stimulates glycolysis Glucagon Source - α-cells of pancreas Increases blood glucose levels Activates the breakdown of glycogen in the liver  Hormonal Control of Carbohydrate Metabolism Epinephrine Source - Adrenal medulla Increases blood glucose levels Stimulates glycogen breakdown in muscles, and to a smaller extent in the liver Blood sugar level depends on the biochemical balance between insulin and glucagon Influenced to some degree by growth hormones and adrenal cortex steroids