Abstract
In Salmonella typhimurium it has been shown that the formation of carbamyl phosphate synthetase [E.C.2.7.2.5], whose gene is encoded by pyrA, is controlled by a cytidine nucleotide and arginine. The synthesis of aspartate transcarbamylase [E.C .2.1.3.2], encoded by pyrB, is controlled primarily by a uridine nucleotide and only slightly by arginine and a cytidine nucleotide. The repressing metabolites for the other four biosynthetic enzymes, namely dihydroorotase ([E.C.3.5.2.3], encoded by pyrC), dihydroorotate dehydrogenase ([E.C.1.3.3.1], encoded by pyrD), orotidine5 '-monophosphate pyrophosphorylase ([E.C.2.4.2.10], encoded by Pyx'S), and orotidine-5'-monophosphate decarboxylase ([E.C.4.1.1.23], encoded by pyrF) have been determined. Specially-constructed strains of S. typhimurium (JL1055, HD1043, and HD1044) were used which lack the enzymes for the interconversion of cytidine and uridine compounds, thus allowing the independent manipulation of endogenous cytidine and uridine nucleotides. Using these strains, a cytidine compound has been shown to be the primary repressing metabolite of dihydroorotase. The remaining three enzymes are repressed primarily by a cytidine nucleotide while a uridine nucleotide aids in repression. The level of phosphorylation of the nucleotide causing repression is most probably at the triphosphate level since high levels of UMP do not cause repression of aspartate transcarbamylase and the levels of UDP are too low to be significant. Thus the level of repression may be stoichiometrically related to the nucleoside triphosphate pools. Indeed, aspartate transcarbamylase is derepressed at UTP concentrations less than 3 mumoles/5 x 10?ü? cells/ml or when the UTP pool level of the total ribonucleoside triphosphates drops below 6 percent. Dihydroorotase is derepressed when the CTP concentration drops below 8 mumoles/5 x 10?ü? cells/ml. The control of synthesis of the pyrimidine enzymes is at the level of transcription. There is no coordinate gene expression for the first three enzymes because they have different effectors of repression whereas the last three enzymes seem to exhibit a coordinate gene expression because they have both a uridine nucleotide and a cytidine nucleotide as repressing metabolites. UMP kinase [E.C.2.7.1._] shows no apparent control by the metabolites tested in these experiments. It is probably synthesized constitutively or it is controlled by other metabolites.
Williams, Jimmy Calvin (1973). Relationship between the level of repression and the amounts of the repressing metabolities of the pyrimidine biosynthetic pathway. Doctoral dissertation, Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -158867.