1887

Abstract

Summary: Sterol side-chain (C-24) methylation was assayed by incorporation of radioactivity from [-C]methionine into the ergosterol fraction in cells of the pathogenic fungi and Methylation at C-24 occurred after nuclear demethylation in all cases. The method was used to measure ergosterol biosynthesis inhibition by the allylamine antimycotics naftifine and SF 86-327, which are known to block squalene epoxidation. In cells treated with SF 86-327 (1 mg 1) to fully inhibit squalene epoxidation, C-24 methylation continued for several hours at about 40% of the control rate. This residual biosynthesis was probably due to methylation of endogenous sterol precursors. The degree of residual biosynthesis in the three fungi correlated well with their susceptibility to SF 86-327. The highly susceptible dermatophyte had negligible residual sterol biosynthesis. These differences were not due to inhibition of methionine uptake. For naftifine (100 mg 1) there was evidence of a second inhibitory action A cell-free assay indicated that this was due to direct inhibition of the C-24 methyltransferase.

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/content/journal/micro/10.1099/00221287-131-7-1595
1985-07-01
2019-12-15
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http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-131-7-1595
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