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Ornithine

Ornithine (also known as 2,5-diaminovaleric acid) is a non-essential amino acid produced by the body. Ornithine occurs in two crystalline forms, namely L(+)-ornithine and DL-ornithine. L-ornithine is an important component of drugs for stimulating liver functions, total amino acid preparations, etc. Salts of L-ornithine are valuable pharmaceutical products. They are useful, e.g., for parenteral nutrition (L-ornithine acetate or L-ornithine monohydrochloride) and the treatment of hepatic diseases (L-ornithine aspartate or L-ornithine-2-ketoglutarate). L-ornithine can replace L-arginine, an amino acid which is essential in infants and children, in all functions. Ornithine is metabolically degraded via three pathways. Ornithine is the substrate for the enzyme ornithine decarboxylase (ODC). ODC action on ornithine results in putrescine required for cell growth and division. From a quantitative point of view this pathway is normally quite insignificant but is important in rapidly dividing cells such as tumor cells. Ornithine decarboxylase (ODC) catalyzes the decarboxylation of L-ornithine to the diamine putrescine. Ornithine carbamyltransferase is an enzyme in a pathway for biosynthesizing arginine, which catalyzes the reaction of forming citrulline by transferring a carbamyl group from carbamylphosphate to ornithine. Putrescine and the polyamines spermidine and spermine are cellular polycations essential for normal cell proliferation and differentiation. ODC expression in mammalian tissues is usually tightly regulated although neoplastic cells often express high levels of the enzyme. Ornithine decarboxylase is one of the key enzymes of polyamine biosynthesis. A reduction in the activity of ODC leads to a reduced polyamine biosynthesis and therefore to reduced polyamine levels in the cell. If inhibition of the activity of this enzyme by ODC inhibitors can be achieved, the polyamine concentration in mammalian cells (including human cells) can be influenced, i.e. lowered, with the aid of such ODC inhibitors. Ornithine is also a substrate for L-Ornithine:2-oxoacid aminotransferase (OAT), a mitochondrial enzyme present in many tissues including liver, kidney, and brain. It catalyzes the transamination of L-ornithine (Orn) to 2-oxoglutarate, producing glutamic gamma-semialdehyde and glutamate. The liver enzyme is believed to function in the intracellular production of proline and the shuttling of carbon skeletons from excess dietary amino acids to the tricarboxylic acid cycle and it has been suggested that OAT competes with ornithine transcarbamylase for Orn and thus limits urea cycle activity. Inhibition of this enzyme can result in an excess of ornithine.

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