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Increasing concentrations of sodium octanoate were progressively inhibitory to the activities of glucokinase, hexokinase, phosphofructokinase, and pyruvate kinase. Glucose-6-phosphate and 6-phosphogluconate dehydrogenases were also markedly inhibited. Other enzymes of carbohydrate metabolism such as lactate dehydrogenase, phosphohexose isomerase, and fructose-1,6-diphosphatase were not decreased. Among the key glycolytic enzymes, the inhibition of pyruvate kinase by the fatty acid was most marked. The biological significance of the inhibition of the key glycolytic enzymes is interpreted as a feedback inhibitory mechanism in regulation of fatty acid biosynthesis. The mechanism may function for rapid adaptation by which the organism can use the fatty acid level as a metabolic directional switch in decreasing glycolysis and turning on gluconeogenesis.

In previous studies we observed that some allyl sulfides can cause increased acetylation of histones and differentiation in DS19 mouse erythroleukemia cells. In the present work we observed increased acetylation of histones with allyl isothiocyanate and butanethiol but not with butyl sulfide or butyl disulfide. Increased acetylation of histones was established by change in electrophoretic mobility, incorporation of [ 3 H]acetate or immunoblotting. Histone deacetylase in nuclei of DS19 cells was inhibited 74% by 0.5 mM allyl mercaptan and 43% by 0.5 mM butanethiol but was not significantly affected by 0.5 mM allyl isothiocyanate. There was some degree of reversibility in the effect of allyl isothiocyanate when the cells were incubated for 15 hr in fresh medium. The data suggested that allyl isothiocyanate may stimulate histone acetylation rather than inhibit histone deacetylation. Addition of allyl isothiocyanate, however, had very little or no additional effect on the induction of histone acetylation caused by trichostatin A. Histone acetyltransferase activity determined in cell homogenates was not increased by preincubation of cells with allyl isothiocyanate or inclusion of allyl isothiocyanate in the assay medium. It was concluded that treatment of mouse erythroleukemia cells with allyl isothiocyanate can cause increased acetylation of histones but the mechanism for this effect requires further elucidation.

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