The first step of histidine biosynthesis.
نویسندگان
چکیده
In a continuation of work on gene-enzyme relationships in histidine biosynthesis (1, 2) we have examined the early steps of the biosynthetic pathway in Salmonella typhimurium. It has been found that the first enzyme of the pathway catalyzes the condensation of 5-phosphoribosyl-1-pyrophosphate and adenosine triphosphate to form pyrophosphate and a product which has been isolated and characterized as N-I-(5’-phosphoribosyl)-ATP (Fig. 1). This enzyme has been named phosphoribosyl-ATP pyrophosphorylase. The reaction is reversible and is very strongly inhibited by histidine. One class of histidine-requiring mutants (Hartman et al. 3, 4) is lacking this enzyme. The conversion of N-l-(5’-phosphoribosyl)-ATP to imidazoleglycerol phosphate, a precursor of histidine (5), is also described. Our investigations stem from the findings of Moyed and Magasanik (6) who first described the enzymatic formation of imidazoleglycerol phosphate in a system containing a bacterial extract, ribose 5-phosphate, an ATP-generating system, glutamine, and Mg++. They demonstrated that ATP was converted to 5-amino-l-ribosyl-4-imidazolecarboxamide-5’-phosphate with the transfer of the purine N-l and C-2 atoms to the ring of imidazoleglycerol phosphate. When glutamine was left out of their system an intermediate of uncertain structure (Compound III)l was accumulated (6). This intermediate seemed to be a bound form of 5-amino-1-ribosyl-4-imidazole-carboxamide-5’phosphate. The formation of Compound III was inhibited by histidine. We have shown that N-l-(5’-phosphoribosyl)-ATP is a precursor of Compound III and can be converted to it. During the course of our investigation, Klopotowski et al. (7) described in extracts of yeast the accumulation of an uncharacterized intermediate between 5-phosphoribosyl-1-pyrophosphate and Compound III. The accumulation of this compound was inhibited by histidine.
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ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 236 شماره
صفحات -
تاریخ انتشار 1961