Regulation of enzymes of the urea cycle and arginine metabolism

Abstract

The urea cycle is comprised of five enzymes but also requires other enzymes and mitochondrial amino acid transporters to function fully. The complete urea cycle is expressed in liver and to a small degree also in enterocytes. However, highly regulated expression of several enzymes present in the urea cycle occurs also in many other tissues, where these enzymes are involved in synthesis of nitric oxide, polyamines, proline and glutamate. Glucagon, insulin, and glucocorticoids are major regulators of the expression of urea cycle enzymes in liver. In contrast, the "urea cycle" enzymes in nonhepatic cells are regulated by a wide range of pro- and antiinflammatory cytokines and other agents. Regulation of these enzymes is largely transcriptional in virtually all cell types. This review emphasizes recent information regarding roles and regulation of urea cycle and arginine metabolic enzymes in liver and other cell types.