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Molecular and Biochemical Features of the Mitochondrial Enzyme Ornithine Transcarbamylase: A Possible New Role as a Signaling Factor

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Abstract:

Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a one-carbon-unit transferring enzyme that synthesizes citrulline using ornithine and carbamoylphosphate as substrates. It is involved in the metabolic transformation of arginine and proline, and it participates in the urea cycle in vertebrates and in the formation of putrescine in plants. Its enzymatic reaction is consistent with a ping-pong mechanism. OTC is expressed in a large variety of organisms from bacteria to mammals. Its gene can be regulated by glucocorticoids and other transcriptional factors such as C/EBP and HNF-4. The functional enzyme exists mostly as a trimer with an approximate molecular weight of 38 kDa. Inborn errors associated with a deficiency of OTC activity cause mainly urea cycle-related disorders, and lead to hyperammonemic states that may become lethal.

In humans and experimental animals, OTC is localized in the mitochondrial matrix, mainly in the liver, but it is also in the intestinal epithelial cells. Some states of hepatotoxicity are associated with hepatocyte disruption and release of OTC into the bloodstream. However, recent evidence suggests that during active cell proliferation (e.g., during liver regeneration), OTC is also released from the hepatic tissue but without apparent damage. In this situation, extracellular and circulating hepatic OTC could be playing a different role, possibly functioning as a signaling molecule.

Keywords: Liver; circulating OTC; enzymatic reaction; mitochondria; protein structure; signaling molecule

Document Type: Research Article

DOI: https://doi.org/10.2174/092986710791331031

Affiliations: Departamento de Biologia Celular, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico (UNAM), Apartado Postal 70-243, Mexico 04510, D.F., Mexico.

Publication date: 2010-07-01

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