PEPCK cytoplasmic

Phosphoenolpyruvate carboxykinase (PEPCK) in the cytoplasm is induced by glucagon and cortisol. It converts OAA to phosphoenolpyruvate (PEP) in a reaction that requires GTP. PEP continues in the pathway to fructose 1,6-bisphosphate. 

A species specificity mi ht be pointed out with respect to the location of PE PC K, an enzyme used for gluconeogenesis, OAA is converted to PEP by PEPCK in the liver Cytoplasm of rats and mice because PEPCK is a cytosolic enzyme in these animals. In the livers of chickens and rabbits, however, OAA is converted to PEP in the mitochondria, because PEKK is mitochondrial in these animals, PEP must then be transported to the cytosol. PEPCK is evenly distributed between the mitochondria and the cytosol in human and cow livers (Pilkis et itf., 1988). 

Pyruvate carboxylase is a mitochondrial enzyme in animal cells, whereas PEPCK is almost exclusively mitochondrial in some species (e.g., pigeons) and cytosolic in others (e.g., rats and mice). In humans (and guinea pigs), PEPCK occurs in both mitochondria and cytosol. An interesting consequence of this species differences is that quinolinate, an inhibitor of cytoplasmic PEPCK, causes hypoglycemia in rats but is less active in humans and guinea pigs. 

For PEPCK to function in gluconeogenesis, oxaloacetate produced in the pyruvate carboxylase reaction in the mitochondria, must be transported to the cytoplasm. PEPCK is not under any known allosteric control. Activity of the enzyme is regulated by hormonal control of its transcription. Glucagon stimulates transcription of the structural gene for PEPCK. Insulin inhibits transcription of the enzyme. By inhibiting PEPCK gene transcription, insulin tends to depress gluconeogenesis rates. 

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