HBG 6 ( Carbohydrate I)

• Carbohydrate Metabolism Assoc Prof Dr Ho Kok Lian, Department of Pathology2 outlines the metabolic fate of pyruvate, the citric acid cycle, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, the metabolism of monosaccharides, and the regulation of blood glucose.
• Glycolysis is the conversion of glucose (6C) to pyruvate (3C) and involves the production of ATP.
• Pyruvate (3C) is converted to acetyl CoA (2C) in the Kreb's Citric acid Cycle/Tricarboxylic acid cycle.
• Acetyl CoA (2C) is converted to CO2 + H2O + Energy (ATP) in the Kreb's Citric acid Cycle/Tricarboxylic acid cycle.
• Glucose is stored as glycogen in the liver and muscle through a process called Glycogenesis.
• Malate dehydrogenase is an enzyme in Kreb's Citric Acid Cycle.
• Enzymes of Kreb's Citric Acid Cycle include Citric synthase, Aconitase, Isocitrate dehydrogenase, a-Ketoglutarate dehydrogenase, Succinate thiokinase, Succinate dehydrogenase, Fumerase, and Malate dehydrogenase.
• a-Ketoglutarate dehydrogenase is inhibited by ATP.
• Fumerase is an enzyme in Kreb's Citric Acid Cycle.
• Regulatory enzymes in Kreb's Citric Acid Cycle include Citrate synthase, which is inhibited by ATP and NADH, and Isocitrate dehydrogenase, which is inhibited by ATP and NADH.
• Mitochondria matrix contains Kreb's Citric Acid Cycle.
• Isocitrate dehydrogenase is activated by ADP.
• Glycogen is broken down into glucose in the liver and muscle through a process called Glycogenolysis.
• Glucose is also stored as a storage form of fat, known as TAG, through a process called Lipogenesis.
• The Pentose phosphate pathway (Hexose monophosphate shunt pathway) converts glucose to F6P.
• The Uronic acid pathway involves the generation of Glucoronic acid and the synthesis of Vitamin C.
• Fructose metabolism and Galactose metabolism are also part of the minor pathways of carbohydrate metabolism.
• Glycolysis is the major pathway of oxidation of glucose found in the cytoplasm of all cells.
• Glycolysis is the principle pathway of glucose metabolism, producing acetyl CoA for oxidation in the Kreb's Citric acid Cycle/Tricarboxylic acid cycle.
• Glycolysis is the main pathway for oxidation of fructose and galactose.
• Glycolysis produces 7 ATP during aerobic condition and 2 ATP during anaerobic condition.
• Glycolysis provides ATP for skeletal muscle under anerobic condition such as vigorous exercise.
• Glucokinase has a high Km for glucose and a sigmoidal curve between glucose and reaction rate.
• Glycolysis provides 2,3 BPG in red blood cells for haemoglobin to unload oxygen at tissues.
• The net yield of Two ATPs per glucose is controlled by Glucokinase, Hexokinase, Phosphofructokinase I, Pyruvate kinase, and Glyceraldehyde 3 - phosphate.
• The conversion of glucose to lactate involves Lactate Dehydrogenase, Glyceraldehyde 3 - phosphate, Pyruvate, Pyruvate kinase, and 2x ADP, 2x ATP.
• Glycolysis allows tissues to survive anoxic (< O 2 ) episodes except heart muscle.
• In the aerobic condition, glucose is converted to 2x pyruvate, while in the anaerobic condition, it is converted to 2x lactate.
• Glucokinase is found in the liver and beta cells of the pancreas.
• The conversion of glucose to pyruvate involves Phosphoglycerate kinase, Pyruvate kinase, and 2x ADP, 2x ATP.
• Hexokinase has a low Km for glucose and a hyperbolic curve between glucose and reaction rate.
• The sequences of reactions for the conversion of glucose to pyruvate involve Triose phosphate isomerase, Glucokinase or Hexokinase, ATP, ADP, Fructose - 6 - phosphate, Phosphohexose - isomerase, Phosphofructokinase I, ATP, ADP, Fructose - 1,6 - bisphosphate, Glyceraldehyde 3 - phosphate, Aldolase A, and Dihydroxyacetone phosphate.
• The reversal of the Glycolysis pathway is used in gluconeogenesis.
• The overall reactions for the conversion of glucose to pyruvate involve 2xADP, 2xATP, 2xATP, 2xADP, 2xNAD, 2xNADH, and 2H+.
• The metabolic significance of Glycolysis is to provide glyceraldehyde - 3 - phosphate for fat synthesis.
• Glycolysis provides the main energy requirement for RBCs, lens, cornea and retina (absence of mitochondria).
• Glycolysis has a high rate of glycolysis in cancer cells causing lactic acidosis and hypoglycemia.
• Feedback inhibition is regulated by G-6-P.
• The metabolic fate of pyruvate can also involve the conversion of pyruvate to alanine, which is then converted to oxaloacetate in the Kreb's Citric Acid Cycle.
• Regulation of Pyruvate Kinase by phosphorylation and dephosphorylation is done by Protein Kinase A and Protein Phosphatase.