Some Folic-mediated Syntheses

Transformylations in purine synthesis have been summarized (Warren e al., 1957) and purine synthesis has been reviewed (Buchanan et al., 1957). Purine synthesis is one of the most important uses of FA, as attested by the findings from a variety of folic-requiring organisms that, in sparing a FA requirement, the efficacy of purines is almost the first to emerge. This may 

In some systems, especially microbial ones, purine synthesis is quite sensitive to antifolics. One would expect that to some extent purines wotild noncompetitively reverse inhibitions by antifolics. Guthrie et al. (1956) found that hypoxanthine or adenine blocks inhibition of Bacillus aubtUis by amethopterin. Also, Tomisek et al. (1958) present evidence that formylation by AICAR is the primary site of amethopterin inhibition in E. coU, and Ghosh et al. (1958) found that some compounds that were competitive antagonists for PGA or CF were not at all inhibitory to Streptococcus faecalis when the PGA was bypassed with adenine plus thymine. 

Phenomena of collateral resistance probably point to multiple sites of action. Two mutants of E. coli resistant to purine antagonists were more resistant than the parent strain to amethopterin (Guthrie et al., 1957). In contrast in Saccharomycea cerevisiae, various folic antagonists, including aminopterin, were reversed by thiamine plus Be purines plus thymine or thymidine were ineffective (McGlohon et al., 1957). These authors suppose that Bi plus Be participate in a pathway of purine synthesis that is less folic-dependent. 

Thymine and thymidine are needed to replace folic acid for Streptococcus faecalis, and cells grown on thymine had no detectable folic acid activity for Lactobacillus casei (Stokes, 1944a,b). The inference was that FA was necessary for the s5mthesis of thymine (or thymidine). The site of the folic reaction was soon recognized to be the 5-methyl carbon. Friedkin and Korn-berg (1957) found that P -labeled deoxyuridylic acid was converted to labeled thymidylic acid by extracts of Escherichia coli. As repeatedly the case in many folic-catalyzed cell-free systems, treatment with Dowex-1 stopped the reaction. It was restored by a boiled extract of E. coli, in turn replaceable by FH4. A preliminary note confirms these results (Greenberg and Humphreys, 1958). 

The conversion of labeled uridine deoxyriboside to thymidine by minced chick embryo or suspensions of bone marrow cells was inhibited by low concentrations of aminopterin, but not the incorporation of labeled thy- 

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