Ornithine transaminase

Ornithine transaminase Wheat Increase of activity Charest Phan, 1990... 

Gyrate atrophy Unclear Ornithine Ornithine transaminase... 

Vigabatrin-induced inhibition of ornithine transaminase has been suggested as an alternative mechanism (49). 

Fig. 2. The incorporation of ammonia derived by a number of pathways, into asparagine in higher plants, a. Nitrate reductase b, nitrite reductase c, nitrogenase .d, glutamine synthetase e, asparagine synthetase f, arginase g, urease h, ornithine transaminase i, glutamate dehydrogenase j, proline dehydrogenase k, transaminases.

Among the numerous enzymes that utilize pyridoxal phosphate (PLP) as cofactor, the amino acid racemases, amino acid decarboxylases (e.g., aromatic amino acids, ornithine, glutamic acid), aminotransferases (y-aminobutyrate transaminase), and a-oxamine synthases, have been the main targets in the search for fluorinated mechanism-based inhibitors. Pharmaceutical companies have played a very active role in this promising research (control of the metabolism of amino acids and neuroamines is very important at the physiological level). 

Arginine Proline Proline oxidase Ornithine-glutamate transaminase Ornithine transcarbamoylase Argininosuccinate synthase Argininosuccinate lyase... 

A transaminase patented by Celgene Corporation (Warren, NJ), called an co-aminotransferase [(co-AT)E.C. 2.6.1.18] does not require an a-amino acid as amino donor instead it requires a primary amine and hence has the ability to produce chiral amines.125 126 A similar co-AT from Vibrio fluvialis has been described for the production of chiral amines along with chiral alcohols when coupled with AdH or chiral amino acids when coupled with an a-amino acid aminotransferase.127130 Another co-AT, ornithine (lysine) aminotransferase (E.C. 2.6.1.68), has been described for the preparation of a chiral pharmaceutical intermediate used in the synthesis of Omapatrilat, a vasopep-tidase inhibitor developed by Bristol-Myers Squibb, as well as the UAA A1 -piperidinc-6-carboxylic acid.131-132... 

Changes in glucose-6-phosphatase, forminoglutamic acid transferase, urocanase, formylase, methyl-H4-folate dehydrogenase, histidiase, glutamic oxalacetic transaminase and carbonyl transferase and ornithine... 

B5. Bickel, H., Hyperornithinaemia due to a defect of ornithine ketoacid transaminase. Proceedings of the Sixth Annvnl Symposium of the Society for the Study of Inborn Errors of Metabolism, Zurich, 1988 pp. 145-146. Livingstone, Edinburgh, 1969. 

Kl. Katunuma, N., Okada, M., Matsuzawa, T., and Otuka, Y., Studies on ornithine keto-acid transaminase. II. Role in metabolic pathway. J. Biochem. Tokyo) 67, 445-449 (1965). 

All of the amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination reactions. Transaminases exist for histidine, serine, phenylalanine, and methionine, but the major pathways of their metabolism do not involve transamination. Transamination of an amino group not at the a-position can also occur. Thus, transfer of 3-amino group of ornithine to a-ketoglutarate converts ornithine to glutamate-y-semialdehyde. 

The most useful, and thus far successful, examples have involved irreversible reactions of nucleophilic functions of an enzyme s reactive site with an enzymatically activated Kcat inhibitor of a Michael-type addition reaction. The activation invariably requires participation of the enzyme s prosthetic group (e.g., flavin of monoamine oxidase) or coenzymes such as pyridoxal (vitamin B) as its phosphate, which is associated with several enzymes (e.g., threonine dehydrase, ornithine decarboxylase, a-ketoglutarate transaminase). 

The soluble and particulate alanine 2-oxoglutarate aminotransferases of tomato fruits (which may be identical proteins) (Rech and Crouzet, 1974 Gazeu-Reyjal and Crouzet, 1976) are estimated to have molecular weights of 100,000 (gel filtration). Some plant transaminases are evidently much smaller. Ornithine 2-oxoacid aminotransferase has a molecular weight estimated at 48,000 (Lu and Mazelis, 1975), and a molecular weight of 56,200 has been determined for L-alanine 5-ketooctanal aminotransferase from Conium maculatum (Roberts, 1977). Although very few estimates are available, and not many alternative methods have been used, it seems clear that the molecular weights of plant transaminases vary considerably from one enzyme to another. They may also differ from comparable animal enzymes (Lu and Mazelis, 1975). 

On a genomic level, transaminases are classified into (up to six) subgroups [1717, 1718], among which group 11 comprises the most useful transaminases, which are able to accept non-a-amino acid t5q)e substrates. Since their natural substrates typically encompass co-aminocarboxylic acids, such as ornithine, lysine, (3-alanine, and co-aminobutyrate, they are commonly denoted as m-trans-aminases (co-TA), in contrast a-transaminases, which only act on a-amino acid-type substrates. 

A -acetylglutamic y-semialdehyde dehydrogenase [4, 7], acetylornithine 5-transaminase [1, 8, 9], acetylornithinase [1, 10, 11], ornithine trans-carbamylase [12], and argininosuccinase [13] have been partially purified and characterized. A -Acetylglutamate synthetase activity has been exhibited in extracts [14], and this enzyme, which catalyzes the first step of the pathway, has been shown in cell suspension experiments to be subject to feedback inhibition by arginine [15],... 

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