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Effects of griseofulvin on dermatophyte metabolism McBride, Barry C.

Abstract

The site of action of griseofulvin is not known. The results of this study enlighten some poorly understood aspects of the mechanism of this problem. Griseofulvin did not interfere with the composition of the free amino acid pool or the nucleic acid precursor pool. Oxidation of exogenous glucose was inhibited by griseofulvin, the extent of inhibition being dependent upon the respiratory characteristics of the mycelial preparation, Griseofulvin altered the pattern of oxidative assimilation of UL-¹⁴C-glucose. More ¹⁴C accumulated in the lipid and cold TCA soluble fraction and less ¹⁴C was accumulated in the hot TCA, hot NaOH, and insoluble residue fractions. A reduced divalent cation concentration induced morphological aberrations similar to those caused by griseofulvin. Coincident with these studies, investigations were made into some aspects of metabolism of uninhibited dermatophytes. Glucose stimulated oxygen uptake, when young cells grown in media with a low carbohydrate concentration were used for micro-respirometer studies. The level of endogenous respiration was affected by exogenous glucose, when glucose stimulated oxygen uptake by less than 14%. M. gypseum oxidizes 50% of the exogenous glucose and assimilates the remainder. A large proportion is assimilated into nitrogenous substances. Cell-free extracts contained glucokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate activity, indicating the presence of the hexose monophosphate shunt.

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