Phosphoenolpyruvate carboxykinase

• OMIM: 261 680
• UniProt: P35558

• OMIM: 261 650
• UniProt: Q16822

Phosphoenolpyruvate carboxykinase [ GTP ] (abbr.: PEPCK ) is that of the enzyme that catalyzes the conversion of oxalacetate to phosphoenolpyruvate by GTP. This reaction step is the rate-determining step in gluconeogenesis. PEPCK is also found in bacteria, in vertebrates there are two isoforms, cytosolic and mitochondrial. They are encoded by the genes in the human PCK1 and PCK2 and particularly expressed in liver, kidney and adipocytes. In contrast to the activity of PEPCK -M PEPCK -C can be regulated by hormones. Mutations in PCK1 or PCK2 can cause the corresponding (rare ) PEPCK deficiency disease.

The PEPCK [ GTP ] is not to be confused with the ATP-dependent PEPCK, which is found in plants and bacteria but not in animals.

Because of their central position in the gluconeogenesis PEPCK is a candidate when it comes to hereditary diabetes or obesity.

Catalyzed reaction

GTP GDP CO2

From GTP a phosphate group is transferred to oxaloacetate and split carbon dioxide. In the active site of the enzyme is an arginine residue, and the metal is manganese in the oxidation state II The keto oxygen forms a complex between arginine and Mn2 , allowing the removal of the carboxyl group at the farther end, forming a double bond. Subsequently, a phosphate of GTP is transferred to the oxygen. At the same time ensures Mn2 and arginine for the complexation of GTP in the enzyme. <

Regulation

The activity of the PEPCK -C, and thus the total of gluconeogenesis, is influenced by a number of hormones. Glucagon helps in the liver by the phosphorylation of a transcription factor, the transcription of the PEPCK, as well as all-trans retinoic acid. Other regulatory molecules are liver lipids, insulin (via SREBP -1c) and γ -interferon.

For the regulation by glucocorticoids see the detailed example there.