Transcarbamylase, aspartic ornithine

Animal and bacterial enzymes that utilize or synthesize carbamyl phosphate have activity with acetyl phosphate. Acyl phosphatase hydrolyzes both substrates, and maybe involved in the specific dynamic action of proteins. Ornithine and aspartic transcarbamylases also synthesize acetylornithine and acetyl aspartate. Finally, bacterial carbamate kinase and animal carbamyl phosphate synthetase utilize acetyl phosphate as well as carbamyl phosphate in the synthesis of adenosine triphosphate. The synthesis of acetyl phosphate and of formyl phosphate by carbamyl phosphate synthetases is described. The mechanism of carbon dioxide activation by animal carbamyl phosphate synthetase is reviewed on the basis of the findings concerning acetate and formate activation. 

Preparations of aspartate transcarbamylase from dog intestinal mucosa, rat liver, E. coli B, and E. coli 185-482 can utilize acetyl-P, although at much slower rates than carbamyl-P. The ratio of carba-myl-P to acetyl-P transfer is of the order of 20 with mammalian enzymes, and 400 with bacterial preparations (as indicated above, the ratios of carbamyl-P to acetyl-P transferring activity are also smaller with mammalian than with bacterial ornithine transcarbamylase). 

The intramitochondrial location of the arginine-specific carbamyl phosphate synthetase in N. crassa has the additional advantage of assuring separate pools of carbamyl phosphate for arginine and pyrimidine biosynthesis (41). Since this precludes the utilization of carbamyl phosphate produced in the course of arginine biosynthesis by aspartate transcarbamylase and of the pyrimidine-specific carbamyl phosphate by ornithine transcarbamylase, the control of these reac-... 

Carbamoyl phosphate (CP) serves as a substrate for two separate transcarbamylase enzymes. One of these, in a reaction with aspartic acid, yields carbamoyl aspartate, the first specific precursor in the UMP pathway the other, in a similar reaction with ornithine, has a similar role for the eventual synthesis of arginine. Thus, CP serves as a common precursor for both UMP and arginine, and special regulation of its formation must be obtained to assure a balanced supply of both end products. The problem is handled in a variety of ways by different organisms. 

Possible hypotheses for the defect in E.v.d.B. are 1. Decreased reutilisation of uracil at the level of uridine phosphorylase or uridine kinase. At low uracil levels reutilisation will predominate over catabolism via the diHPyDH reaction and at high uracil concentrations the reverse will be the case presumably. 2. Increased synthesis of pyrimidines due to a fluctuating regulation at the level of aspartate transcarbamylase and/or ornithine trans-carbamylase. It has to be presumed that attacks of periodic hyperammonemia have not occurred during the limited time of investigations, with the phenomena of patient A.G. in mind. 

Similar investigations with another series of enzymes were carried out on B. subtilis (Donachie, 1965). He studied yet another group of enzymes (aspartate-transcarbamylase, ornithine-transcarbamylase, alkaline phosphatase) from this point of view, comparing their activity with the dynamics of DNA synthesis. Well-defined "steps" in enzyme synthesis were observed in the case of aspartate-transcarbamylase (Fig. 38). The dynamics of synthesis of the other enzymes was less clear because of their rapid breakdown after synthesis. All this shows that activity of synthesis of a particular enzyme is definitely dependent upon the number of active genes. 

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