02-Carbohydrate metabolism 2023-24.pdf

Dr.Shamim Shaikh Mohiuddin Assistant Professor Dept OF Biochemistry College of Medicine, IAU Overview -Glucose is the central molecule for carbohydrate metabolism. -Fructose and Galactose enter the pathways at various points of metabolism. -All cells can utilize glucose for energy production. -G...

Dr.Shamim Shaikh Mohiuddin Assistant Professor Dept OF Biochemistry College of Medicine, IAU Overview -Glucose is the central molecule for carbohydrate metabolism. -Fructose and Galactose enter the pathways at various points of metabolism. -All cells can utilize glucose for energy production. -Glucose uptake from blood to cells usually mediated by insulin and transporters. -Liver is central site for carbohydrate metabolism and it monitor and stabilized the blood glucose level. -Fasting blood glucose level in normal individual is 70-100 mg/dl Major pathways of carbohydrate metabolism 1. Glycolysis - Oxidation of glucose to pyruvate and lactate 2. Citric acid cycle (Krebs cycle or TCA cycle) - The oxidation of acetyl CoA to CO2 3. Gluconeogenesis - Formation of glucose from non-carbohydrate precursors eg. Amino acids, glycerol and lactate 4. Glycogenesis - Formation of glycogen from glucose 5. Glycogenolysis - The breakdown of glycogen to glucose 6. Hexose monophosphate shunt - Alternative pathway to glycolysis and TCA cycle for oxidation of glucose to CO2 and water  Fates of Glucose 1. Fed state A. Storage as glycogen in -Liver -Skeletal muscle B. Storage as lipids in -Adipose tissue 2. Fasted state A. Metabolized for energy B. New glucose synthesized Immediately after eating a meal………. Four major metabolic pathways: -Immediate source of energy -Pentophosphate pathway -Glycogen synthesis in liver/muscle -Precursor for triacylglycerol synthesis  Glycolysis -Defined as sequence of reactions that converts glucose or glycogen into pyruvate or lactate with production of ATP. Major features of glycolysis 1. Glycolysis takes place in all cells of the body. The enzymes for this pathway present in the cytoplasm of the cells. 2. Two types a. Aerobic- In presence of oxygen - Pyruvate is formed which is further oxidized to CO2 and water b. Anaerobic- In absence of oxygen - Lactate is the end product(RBC) - Ethanol is the end product (Anaerobic microorganism) 3. Glycolysis is a major pathway for ATP synthesis in tissues lacking mitochondria e.g. erythrocytes, cornea and lens of the eye. 4. Glycolysis is essential for brain which depends on glucose for energy Steps of Glycolysis Glucose + 2 ADP + 2 Pi 2 Pyruvate + 2 ATP + 2 H2O Production of ATP in glycolysis Under anaerobic condition- 2 ATP Under aerobic condition- 38 ATP Citric acid cycle(TCA cycle) Citric acid cycle essentially involves the oxidation of acetyl CoA to CO2 and H2O Major features 1. Central pathway connecting almost all individual metabolic pathways either directly or indirectly 2. The enzymes of TCA cycle are located in mitochondrial matrix 3. TCA cycle basically involves the combination of 2 carbon acetyl CoA + 6 carbon Tricarboxylic acid citrate 4 carbon oxaloacetate Energetics of TCA cycle Total 12 ATP are produced from one acetyl CoA One molecule of NADH is equivalent to 3 ATP One molecule of FADH2 is equivalent to 2 ATP TCA cycle  Complete oxidation of glucose Substrate phosphorylation Electron transport chain (ETC) (Formation of ATP without ETC) 6ATP (2NADH) Glycolysis 2 ATP 8 ATP 2Pyruvate - 6ATP (2NADH) 2acetylCoA 6 ATP TCA cycle 2 ATP (2 acetylCoA) 18 ATP (6NADH) 24 ATP 4ATP (2FADH2) Oxidation of one molecule of glucose 38 ATP Gluconeogenesis The synthesis of glucose from non carbohydrate compound is known as gluconeogenesis -The major substrate for gluconeogenesis are…… Lactate Glucogenic amino acids Glycerol - Gluconeogenesis is mainly occurs in liver and to some extent in kidney matrix Importance of gluconeogenesis 1. Brain, CNS, erythrocytes and kidney medulla are dependent only on glucose for continuous supply of energy 2. Under anaerobic condition glucose is the only source that supplies energy to the skeletal muscle 3. In prolonged fasting condition gluconeogenesis must occur to meet the basal requirement of body for glucose Glycogenesis -The process of synthesis of glycogen from glucose is known as glycogenesis -Occurs mainly in muscle and liver cell -The reaction : Glucose Glucose-6-P Hexokinase / Glucokinase Glucose-6-P Glucose-1-P Phosphoglucomutase Glucose-1-P + UTP UDPG + Pyrophosphate UDPG Pyrophosphorylase -Glycogen synthase catalyzes the formation of α-1,4-glucosidic linkage in glycogen Branching enzyme catalyzes the formation of α-1,6-glucosidic linkage in glycogen Finally the branches grow by further additions of 1 → 4-gucosyl units and further branching (like tree!) Glycogenolysis The breakdown of stored glycogen in liver and muscle is known as glycogenolysis Process….. a. Glycogen phosphorylase catalyzes cleavage of the 1→4 linkages of glycogen to yield glucose-1-phosphate. b.Debranching enzyme hydrolysis of the 1→6 linkages. c. The combined action of these enzyme leads to the complete breakdown of glycogen.  1,4 linkage 1,6 linkage Glycogen phosphorylase 1,6 linkage Debranching enzyme Process of Glycogenolysis Hexose monophosphate shunt - It is also called as pentose phosphate pathway. - It is an alternative pathway to glycolysis and TCA cycle for the oxidation of glucose. - It is concerned in biosynthesis of NADPH and pentose. - Liver, adipose tissue, adrenal gland, erythrocytes, testes and lactating mammary gland are highly active for HMP shunt. - The enzymes of HMP shunt are located in cytosol. - It does not generate ATP but has two major function : 1. The formation of NADPH synthesis of fatty acid and steroids 2. The synthesis of ribose nucleotide and nucleic acid formation HMP SHUNT