| Abstract: | It was found that in the livers of db/db mice with hyperinsulinemia, obesity and non-insulin-dependent diabetes the rates of cholesterol biosynthesis from pyruvate and, to a lesser extent, from acetate and mevalonate as well as of cholesterol ester biosynthesis from pyruvate (but not from acetate and mevalonate) are increased. Presumably, the observed changes are mediated by structural alterations in the CoA reserves, i.e., increase of free CoA to short-chain acyl-CoA and free CoA to long-chain fatty acyl-CoA indices, and of the ratio between enzymatic activities of generation and utilization of NADPH. Treatment of db/db mice with phosphopantothenate, besides eliciting changes in the CoA reserves structure towards normalization and inhibition of NADP-dependent dehydrogenases and pyruvate and 2-oxoglutarate dehydrogenase complexes, causes the diminution of cholesterol and its ester levels in the liver in the absence of any conspicuous changes in the rates of their biosynthesis from pyruvate. |
