Gluconeogenesis (glucose from non carbohydrate sources) pptx

Describes the formation of glucose from non carbohydrate sources, initiating with pyruvate

1. Gluconeogenesis

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.

9. Harper’s 31 st P173

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

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