Glucose Metabolism Lecture 4 PDF

Introduction of Glucose Metabolism Lecture-4 GLUCONEOGENESIS  GLUCONEOGENESIS Muscle proteins may break down to supply amino acids. These are transported to liver where they join gluconeogenesis. Three Glycolysis reactions are essentially irreversible....

Introduction of Glucose Metabolism Lecture-4 GLUCONEOGENESIS  GLUCONEOGENESIS Muscle proteins may break down to supply amino acids. These are transported to liver where they join gluconeogenesis. Three Glycolysis reactions are essentially irreversible.  Hexokinase (or Glucokinase)  Phosphofructokin ase  Pyruvate Kinase. These steps must be bypassed in Gluconeogenesis. Unique key enzymes of gluconeogenesis Reactions 1, 2, 3 & 4 are catalyzed by enzymes NOT used in glycolysis 1- Pyruvate to oxalacatate GLUCOSE by pyruvate carboxylase 2- oxalacetate to phosphoenol pyruvate by PEP carboxykinase GLUCONEOGENESIS 3- Fructose 1,6 bisphosphate to fructose 6 phosphate by fructose 1,6 bisphosphatase 4- Glucose 6-phosphate to glucose by glucose 6-phosphatase Other reactions of gluconeogenesis are catalyzed by same enzymes of glycolysis in the reverse direction Gluconeogenesis irreversible Glycolytic irreversible enzymes enzymes glucose-6-phosphatase-1 Glucokinase ,-1 hexokinase Fructose 1-6-2 phospho-fructo-2 diphosphatase kinase -1 pyruvate carboxylase ,-3 Pyruvate kinase-3 PEP carboxykinase  Gluconeogenic precursors = substrates used for glucose synthesis 1- Intermediates of glycolysis 2- Intermediates of citric acid cycle : are converted to oxalacetate then to glucose 3- Lactate Lactic acid formed of anaerobic glycolysis in cells as RBCs & extensive exersicing skeletal muscles are transported in blood to liver to be converted to pyruvate then to glucose (Cori cycle) 4- Glycerol Glycerol is derived from the lipid triacylglycerol in adipose tissue. Glycerol is converted into dihydroxyacetone phosphate (DHAP) then to glucose. 5- Glucogenic amino acids of proteins Glucogenic amino acids are deaminated to form α-ketoacids α-keto acids are converted to pyruvate or intermediates of citric acid cycle then to glucose  Cori cycle LIVER MUSCLE Glucose Glucose Gluconeogenesis Glycotysis BLOOD Pyruvate Pyruvate +H+ NADH +H+ NADH Lactate Lactate dehydrogenase dehydrogenase + + NAD NAD Lactate Lactate Fig. 8.84 : TheCoricycle Importance 1-It prevents loss of lactic acid as a waste product in urine. It supplies RBCs and contracting muscles with glucose for utilization and ATP-2.production Glucogenic Amino Acids  Clinical application of gluconeogenesis 1. Fructose 1,6 bisphosphatase deficiency -Both are characterized by Fasting Hypoglycemia and Lactic acidosis. -Treatment : feed high CHO diets and avoidance of fasting 2-Hypoglycemia in neonates - Premature babies are more susceptible to hypoglycemia. - They have immature nonfunctional enzymes for gluconeogenesis and low adipose tissue mass.