Gluconeogenesis
- 1. Gluconeogenesis Dr. Farhana Atia Associate Professor Department of Biochemistry Nilphamari Medical College, Nilphamari
- 2. GLUCONEOGENESIS • Formation of glucose or glycogen from non carbohydrate precursor is called gluconeogenesis Importance of Gluconeogenesis: • Maintain blood glucose concentration during fasting, starvation & limited carbohydrate intake. This is necessary especially for the nervous system & erythrocytes
- 3. Importance of gluconeogenesis • Failure of gluconeogenesis is usually fatal. Hypoglycemia causes brain dysfunction, which can lead to coma & death • Maintain adequate concentration of intermediates of citric acid cycle • Clear the product of metabolism of other tissue from blood. Example-Lactate produced in muscle & RBC, glycerol continuously produced in adipose tissue • Excessive gluconeogenesis occurs in critically ill patients in response to injury & infection, contributing to hyperglycemia
- 4. Salient features • Substrate: Glucogenic amino acid Lactate Glycerol Fatty acid Pyruvate Intermediates of TCA cycle Propionates • Product: Glucose • Site : • Liver (90%) • Kidney (10-40%) • Intestine • Compartment : Cytoplasm & mitochondria • Nature : Anabolic
- 5. Glucogenic Amino Acids All amino acid except lysine & leucine
- 6. Steps of Gluconeogenesis • It involves glycolysis, the citric acid cycle and some other reactions • Glycolysis and gluconeogenesis share the same pathway but in opposite directions • Three nonequilibrium reactions in glycolysis prevent simple reversal of glycolysis. The reactions are catalyzed by- • Hexokinase • Phosphofructokinase • Pyruvate kinase
- 7. Steps of Gluconeogenesis • The reactions are reversed as follows- Reaction catalyzed by pyruvate kinase: Reversal involves two endothermic reaction • Pyruvate carboxylase in mitochondria catalyzes carboxylation of pyruvate to oxaloacetate • Phosphoenolpyruvate carboxykinase in cytosol catalyzes decarboxylation & phosphorylation of oxaloacetate to phosphoenolpyruvate
- 8. Steps of Gluconeogenesis Reaction catalyzed by phosphofructokinase: The conversion of fructose 1,6-bisphosphate to fructose-6- phosphate is catalyzed by fructose 1,6- bisphosphatase Reaction catalyzed by hexokinase: The conversion of glucose-6-phosphate to glucose is catalyzed by glucose-6-phosphatase. It is present in liver & kidney but absent from muscle, which cannot export glucose into bloodstream.
- 10. Regulation of gluconeogenesis • Glucagon & epinephrine • Substrate availability • Enzyme • Pyruvate carboxylase • PEP carboxykinase • Fructose 1,6 bis-phosphatase • Glucose 6 phosphatase
- 11. Cori Cycle/ Lactic Acid Cycle • Glucose is formed from 2 groups of compounds via gluconeogenesis • Amino acids involve in direct net conversion • Product of metabolism of glucose in tissue • Thus, lactate, formed by glycolysis in skeletal muscle & RBC, is transported to the liver & kidneys where it reforms glucose • Which again becomes available via the circulation for oxidation in the tissues. This process is known as Cori cycle.
- 12. Glucose-alanine cycle • In fasting state there is considerable output of alanine from skeletal muscle. • It is formed by transamination of pyruvate produced by glycolysis of muscle glycogen & is exported to the liver • There after transamination back to pyruvate & becomes a substrate for gluconeogenesis. This glucose-alanine cycle provides an indirect way of utilizing muscle glycogen to maintain blood glucose in the fasting state