Aspartate transcarbamylase enzyme, pyrimidine pathway

As with purines, there is indirect evidence from studies in vitro that regenerating tetrathyridia of M. corti can synthesise pyrimidines de novo (315). Furthermore, aspartate transcarbamylase, the first enzyme in the pathway, has been demonstrated in Moniezia benedini (39), while five of the six pathway enzymes have been measured in H. diminuta (326). It appears, therefore, that at least some cestodes have the capacity to synthesise pyrimidines by the biosynthetic route. Little is known of pyrimidine salvage pathways in cestodes, although the key enzyme thymidine kinase has been... 

Belkai d, M., Penverne, B., Denis, M., and Herve, G. (1987). In situ behavior of the pyrimidine pathway enzymes in Saccharomyces cerevisiae. 2. Reaction mechanism of aspartate transcarbamylase dissociated from carbamylphosphate synthetase by genetic alteration. Arch. Biochem,. Biophys., 254, 568-578. 

The utilization of ammonia resulting from the combination of carbamyl phosphate with aspartic acid, the initial reaction for the synthesis of the pyrimidine nucleotides, continues only as long as there is a requirement for them (Fig. 3). Regulation of this biosynthetic pathway is probably by way of feedback inhibition of aspartate transcarbamylase. The rat liver enzyme is inhibited by uridine, cytidine or thymidine or such derivatives as CMP, UTP, or TMP, all intermediates or products of this pathway (B8). This is not the only enzyme of the pathway which may be subject to feedback regulation. Dihydroorotase from rat liver is also inhibited by some pyrimidines and purines (B9). 

If the auxotroph has only a partial requirement, growth in minimal medium will be slow and derepression of the pathway enzymes will result. Thus, growth of a leaky pyrimidine auxotroph in minimal medium leads to a SOO-fold increase in aspartate transcarbamylase (Moyed, 1961b). 

Aspartate transcarbamylase (ATCase) catalyzes the formation of carbamoyl aspartate with CP and aspartic acid as substrates. It is the first specific enzyme for the pyrimidine pathway, and it holds a special place in the historical development of end-product control at this level. The concept of feedback inhibition as an important regulatory mechanism evolved from the initial discovery by Yates and Pardee [90] that CTP is a potent inhibitor of ATCase. It has since developed into a prototype for a regulatory protein with classic allosteric properties. A thorough characterization of the enzyme and its properties has been made through the combined efforts of Gerhart, Pardee, Schachman, and Changeux [91-97]. A summary of these studies follows. 

First three enzymes of the pyrimidine nucleotide pathway Carbamylphosphate synthetase aspartate transcarbamylase dihydro-orotase (Coleman et al., 1977)... 

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