J4 Gluconeogenesis

Pyruvate is converted to oxaloacetate (by pyruvate carboxylase). The oxaloacetate is decarboxylated and phosphorylated to phosphoenolpyruvate (PEP) by phosphoenolpyruvate carboxykinase (PEP carboxykinase). PEP is converted to fructose 1,6-bisphosphate by a direct reversal of several reactions in glycolysis. Next, fructose 1,6-bisphosphate is dephosphorylated to fructose 6-phosphate (by fructose 1,6-bisphosphatase) and this is then converted to glucose 6-phosphate (by phosphoglucoisomerase). Finally, glucose 6-phosphate is dephosphorylated (by glucose 6-phosphatase) to yield glucose. 

The synthesis of one molecule of glucose from two molecules of pyruvate requires six molecules of ATP. 

Oxaloacetate, the product of the first step in gluconeogenesis, must leave the mitochondrion and enter the cytosol where the subsequent enzyme steps take place. Since the inner mitochondrial membrane is impermeable to oxaloacetate, it is converted to malate by mitochondrial malate dehydrogenase. This leaves the mitochondrion and is converted back to oxaloacetate in the cytosol by cytoplasmic malate dehydrogenase. 

Oxaloacetate, the product of the pyruvate carboxylase reaction, functions both as an important citric acid cycle intermediate in the oxidation of acetyl CoA and as a precursor for gluconeogenesis. The activity of pyruvate carboxylase depends on the presence of acetyl CoA so that more oxaloacetate is made when acetyl CoA levels rise. 

Instant Notes in Biochemistry 2nd Edition, B.D. Hames N.M. Hooper, (c) 2000 BIOS Scientific Publishers Ltd, Oxford. 

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