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Phospho enol pyruvate carboxy kinase- Reaction catalyzed and significance- Semester Paper
Phospho enol pyruvate carboxy kinase- This is an enzyme of pathway of gluconeogenesis. Gluconeogenesis involves the formation of Glucose or Glycogen from non carbohydrate precursors.The major substrates are the glucogenic amino acids, lactate, glycerol, and propionate. These noncarbohydrate precursors of glucose are first converted into pyruvate or enter the pathway at later intermediates such as oxaloacetate and Dihydroxyacetone phosphate. In glycolysis, glucose is converted into pyruvate; in gluconeogenesis, pyruvate is converted into glucose. However,gluconeogenesis is not a reversal of glycolysis.
Phosphoenol pyruvate is formed from pyruvate by way of oxaloacetate through the action of pyruvate carboxylase and phosphoenolpyruvate carboxykinase.
Mitochondrial pyruvate carboxylase catalyses the carboxylation of pyruvate to oxaloacetate, an ATP-requiring reaction in which the vitamin biotin is the coenzyme. Biotin binds CO2 from bicarbonate as carboxybiotin prior to the addition of the CO2 to pyruvate.
Pyruvate carboxylase is a mitochondrial enzyme, whereas the other enzymes of gluconeogenesis are cytoplasmic.
Oxaloacetate, the product of the pyruvate carboxylase reaction, is reduced to malate inside the mitochondrion for transport to the cytosol. The reduction is accomplished by an NADH-linked malate dehydrogenase. When malate has been transported across the mitochondrial membrane, it is reoxidized to oxaloacetate by an NAD+-linked malate dehydrogenase in the cytosol.
Figure- showing the transportation of oxaloacetate outside the mitochondrion in the form of Malate
Phosphoenol pyruvate carboxykinase, catalyzes the decarboxylation and phosphorylation of oxaloacetate to phosphoenol pyruvate using GTP as the phosphate donor. In liver and kidney, the reaction of succinate thiokinase in the citric acid cycle produces GTP (rather than ATP as in other tissues), and this GTP is used for the reaction of phosphoenolpyruvate carboxykinase, thus providing a link between citric acid cycle activity and gluconeogenesis, to prevent excessive removal of oxaloacetate for gluconeogenesis, which would impair citric acid cycle activity.
Glucagon, which rises during starvation stimulates the production of phosphoenolpyruvate carboxykinase to increase the rate of gluconeogenesis.