Lipogenesis from ketone bodies in rat brain. Evidence for conversion of acetoacetate into acetyl coenzyme A in the cytosol

Abstract

The metabolism of acetoacetate via a proposed cytosolic pathway in brain of 1 week old rats was investigated. (-) Hydroxycitrate, an inhibitor of ATP citrate lyase, markedly inhibited the incorporation of carbon from labelled glucose and 3 hydroxybutyrate into cerebral lipids, but had no effect on the incorporation of labelled acetate and acetoacetate into brain lipids. Similarly, n butylmalonate and benzene 1,2,3 tricarboxylate inhibited the incorporation of labelled 3 hydroxybutyrate but not of acetoacetate into cerebral lipids. These inhibitors had no effect on the oxidation to 14CO2 of the labelled substrates used. (-) Hydroxycitrate decreased the incorporation of 3H from 3H2O into cerebral lipids by slices metabolizing either glucose or 3 hydroxybutyrate, but not in the presence of acetoacetate. (-) Hydroxycitrate also differentially inhibited the incorporation of [2 14C] leucine and [U 14C]leucine into cerebral lipids. The data show that, although the acetyl moiety of acetyl CoA generated in brain mitochondria is largely translocated as citrate from these organelles to the cytosol, a cytosolic pathway exists by which acetoacetate is converted directly into acetyl CoA in this cellular compartment.