Glucose-6-phosphate Dehydrogenase from Rat Liver II. Effect of Diet on Enzyme Activity in vivo, and Inhibition by Long Chain Fatty Acids in vitro

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Abstract
The rat liver glucose-6-phosphate dehydrogenase [EC 1.1.1.49] activity was increased on re-feeding animals after two days of fasting. The extent of the increment in the enzyme activity was inversely related to the fat content of the diet. Dietary experiments indicated that unsaturated fatty acids were more effective than saturated fatty acids in suppressing the enzyme induction. Glucose-6-phosphate dehydrogenase purified from rat liver was inhibited by the free fatty acids, myristic, lauric and palmitic acids in decreasing order. Glucose-6-phosphate dehydrogenase was specifically protected from the inhibition by free fatty acids in the presence of NADP, and, to a lesser extent, in the presence of glucose 6-phosphate. ATP, GTP and ITP facilitated the inhibitory effect of fatty acids, and the effect of ATP was abolished by ADP or AMP. The facilitatory effect of ATP was more significant at high pH values. The transition temperature of glucose-6-phosphate dehydrogenase was markedly lowered by free fatty acids or ATP and elevated by NADP. Free fatty acid disaggregated the active enzyme into inactive subunits. The inhibition of glucose-6-phosphate dehydrogenase in vivo by free fatty acids was discussed and it was suggested that the fatty acid synthesis was controlled in two ways by free fatty acids: one by inhibiting acetyl-CoA carboxylase [EC 6.4.1.2], and the other by restricting the supply of NADPH through the inhibition of glucose-6-phosphate dehydrogenase.