Aspartate carbamyl transferase

I. Carbamyl Phosphate-Aspartate Transcarbamylase (Aspartate Carbamyl Transferase)... 

The operation of the feedback mechanism in the cell can be described in the following manner if nucleic acid syntheris were proceeding at a rapid rate, the concentration of nucleotides in the cell, e.g. CMP, would decrease, relieve aspartate-carbamyl transferase (also called carbamyl-aspartic acid synthetase) reaction of any inhibition, and thus permit an increased rate of pyrimidine biosyntheris. If nucleic acid syntheris were slowed or halted, the CMP concentration would rise, inhibit the enzyme, and thereby decelerate pyrimidine biosynthesis. 

Cases are known, however, where Drosophila genes coding for one family of isozymes are linked. The classical example is the rudimentary locus (1-54.5). This locus contains genes which control the synthesis of the functionally related enzymes aspartate carbamyl transferase (ACT), carbamyl phosphate synthetase... 

In other cases we encounter not induction but repression of enzyme synthesis by a metabolite in whose synthesis the enzyme is concerned (the same may also be inhibited in its activity by other components of the reaction sequence in which it it involved, see p. 252). The enzyme whose activity is lost or markedly reduced is not necessarily that which completes the synthesis of the repressor molecule (i.e. not that catalysing the last reaction of the biosynthetic pathway). For instance, uracil can suppress, in certain strains of the bacterium, Escherichia coU, the activity of the enzyme aspartate carbamyl-transferase which promotes the interaction between aspartic acid and carbamyl phosphate, a reaction which is the first step in the reaction sequence involved in pyrimidine biosynthesis. Further, the experimental evidence indicates that the uracil acts as a repressor by preventing synthesis of the enzyme. 

Studies of the mechanism of end-product inhibition have revealed that the configuration and activity of certain enzymes can be modified by combination with substances "effectors ) unrelated to their substrates. The effector binds to a site(s) separate from that involved in substrate-enzyme combination and in so doing alters the configuration of the enzyme, e.g. by altering the degree of aggregation of the sub-units of the enzyme molecule. Such enzymes are described as allosteric enzymes. Aspartic acid can be the precursor of pyrimidine bases and the first reaction involves the allosteric enzyme aspartate carbamyl-transferase. This enzyme is inhibited by one of the end-products, cytidine triphosphate (CTP). Clearly there is consider-... 

Treatment of aspartate carbamyl-transferase with heat, with ions... 

The liver appeared to be a target organ for hexachloroethane following oral administration. When one dose of 500 mg/kg was administered in an olive oil aqueous emulsion to male sheep, the levels of glutamate dehydrogenase, sorbitol dehydrogenase, ornithine carbamyl transferase, and aspartate aminotransferase in serum increased in the 2-day period after compound administration and then normalized (Fowler 1969b). Hexachloroethane had no effect on bromsulphthalein uptake from the blood by liver cells, but the transfer of this dye to bile was reduced in sheep exposed to doses of 500-1,000 mg/kg/day. 

Exposure of male Fischer 344 rats to ptzra-xylene (0-1600 ppm [0-6940 mg/m- ], 6 h per day for one or three days) had negligible effect on hepatic morphology and serum activities of alanine or aspartate aminotransferases, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase or serum bilirubin concentration (Simmons et al., 1991). Liver size was increased and its cytochrome P450 content was elevated. 

The biomolecular modes of action of ornithine have been the subject of several experimental investigations. Ornithine activates the enzymes carbamylphosphate synthetase and ornithine carbamyl transferase, which are necessary for the liver-specific process of urea synthesis (133,139) this occurs mainly in the periportal hepa-tocytes (= definitive ammonia detoxification). Glutamine synthesis (binding of ammonia to glutamate) takes place predominantly in the perivenous hepatocytes (= transitory ammonia detoxification). Large amounts of glutamate are necessary for this. Aspartate, ornithine... 

Serum liver enzymes are elevated, including aspartate transaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (AP), ornithine carbamyl transferase, and isocitric dehydrogenase. 

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