Ornithine, carboxyl activation

Amino Acid Conjugation. In the second type of acylation reaction, exogenous carboxylic acids are activated to form S-CoA derivative in a reaction involving ATP and CoA. These CoA derivatives then acylate the amino group of a variety of amino acids. Glycine and glutamate appear to be the most common acceptor of amino acids in mammals in other organisms, other amino acids are involved. These include ornithine in reptiles and birds and taurine in fish. 

Fig. I. Metabolic map for synthesis and metabolism of glutamate and aspartate. AAT = aspartate aminotransferase AS = asparagine synthetase GAD = glutamic acid decarboxylase GDH = glutamate dehydrogenase GS = glutamine synthetase OAT = ornithine D-aminotransferase P5CDH = l-pyrroline-5-carboxylate dehydrogena.se PAG = phosphate-activated glutaminase PO = proline oxidase TCA = tricarboxylic acid.

Proline (3) is derived biosynlhetically from glutamic acid (67). This dicarboxylic acid is activated with ATP and tiien reduced to the corresponding semialdehyde, which spontaneously cyclizes to ALpyrroline-5-carboxylic acid and is reduced to proline by reduced NAD. Ornithine can be directly converted to 4-glutamylsemialdehyde, providing another route to proline. 

Unexpectedly, the R1 chimera had sensitivity to the E. coli allosteric activator, ornithine. However, the x-ray structure (26) subsequently showed that ornithine is not bound exclusively to the regulatory subdomain, but rather bridges the catalytic and regulatory subdomains. These experiments clearly demonstrated that the mammalian allosteric effectors bind to B3, a separately folded regulatory subdomain located at the carboxyl end of CPS.B. 

As a redox couple, proline and pyrroline-5-carboxylate provide a mechanism for the intercompartmental and intercellular transfer of redox potential. The transfer of redox potential alters the ratio of NADP /NADPH thereby activating certain metabolic pathways. Although the reduction of pyrroline-5-carboxylate is the central mechanism in the transfer of redox potential, the metabolic interconversions of proline, ornithine, and glutamate with pyrroline-5-carboxylate as the obligate intermediate also may play a role. The endpoint of this regulation appears to be the formation of purine ribonucleotides by both salvage and de novo mechanisms. Proline and pyrroline-5-carboxylate appear to be metabolic signals which can be fine-tuned by humoral factors to coordinate the metabolism of amino acids and ribonucleotides. When the transfer is from cell to cell, proline and pyrroline-5-carboxyl-ate can function as intercellular communicators. 

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