Gluconeogenesis in Fasting state is indicated by
Ans is 'b' i.e. Pyruvate Carboxylase activation by Acetyl CoA "Allosteric activation of hepatic pyruvate carboxylase by acetyl CoA occurs during fasting. As a result of excessive lipolysis in adipose tissue, the liver is flooded with fatty acids. The rate of formation of acetyl CoA by f-oxidation of these fatty acids exceeds the capacity of the liver to oxidize it to CO2 and H2O. As a result, acetyl CoA accumulates and leads to activation of pyruvate carboxylase. Acetyl CoA also inhibits pyruvate dehydrogenase. Thus, this single compound can divert pyruvate toward gluconeogenesis and away from the TCA cycle. Lippincott BiochemistryGluconeogenesis is not simple reversal of glycolysis. There are 10 reactions in glycolysis. Seven of these glycolytic reactions are reversible and are used in the synthesis of glucose from lactate or pyruvate. However, three of the reactions are irreversible. These 3 reactions are circumvented by four alternate reactions.The 3 irreversible reactions of Glycolysis are:Phosphorylation of Glucose to Glucose -6-phosphate by HexokinasePhosphorylation of Fructose-6-phosphate to Fructose 1, 6 -bisphosphate by Phosphofructokinase-1.Conversion of Phosphoenolpyruvate to Pyruvate by Pyruvate kinaseThe reactions unique to gluconeogenesis which circumvent these 3 irreversible reactions are:Pyruvate to Phosphoenolpyruvate by 2 reactions:Pyruvate is carboxylated to Oxaloacetate by Pyruvate carboxylase.Oxaloacetate is converted to Phosphoenolpyruvate by enzyme Phosphoenolpyruvate carboxykinase (PEP carboxykinase).Conversion of Fructose 1, 6-Bisphosphate to Fructose 6-phosphate catalyzed by Fructose 1, 6-bisphosphataseConversion of Glucose 6-phosphate to glucose catalyzed by glucose 6-phosphatase.Since Glycolysis and Gluconeogenesis share the same pathway but in opposite directions, they are regulated reciprocally.Allosteric regulation:Allosteric regulation by acetyl CoAPyruvate carboxylase is allosterically activated by acetyl CoA. .During fasting large amounts of acetyl CoA derived from oxidation of fatty acids, inhibits pyruvate dehydrogenase and activates Pyruvate carboxylase. Thus, acetyl CoA diverts pyruvate toward gluconeogenesis and away from the TCA cycle.Allosteric regulation by AMPFructose 1, 6-bisphosphatase is inhibited by AMP--a compound that activates phosphofructokinase. Elevated AMP thus stimulates glycolytic pathway that oxidize nutrients to provide energy for the cell. (AMP signals "energy-poor" state in the cell.) Conversely, low concentrations of AMP and high levels of ATP stimulate gluconeogenesis.Allosteric regulation by Fructose 2, 6-bisphosphate:Fructose 2, 6-bisphosphate is allosteric inhibitor of fructose 1, 6-bisphosphatase and activator of phosphofructokinase-1.The concentration of fructose 2, 6-bisphosphate is influenced by the levels of circulating glucagon.When there is abundant supply of glucose, the concentration of fructose 2, 6-bisphosphate increases, stimulating glycolysis by activating phosphofructokinase-1 and inhibiting fructose 1, 6-bisphosphatase.The gluconeogenesis pathway. The numbered reactions are unique to gluconeogenesis.In the fasting state Glucagon levels increase. Glucagon lowers the level of fructose 2, 6-bisphosphate, resulting in activation of fructose 1, 6-bisphosphatase and inhibition of phosphofructokinase, thus favoring gluconeogenesis over glycolysis.
Citrate activation by acetyl co-a carboxylase
Pyruvate Carboxylase activation by Acetyl CoA
Fructose 1,6 bisphosphate activates Pyruvate Kinase
Fructose 2,6 bisphosphate activates PFK-1
Gluconeogenesis