Lipogenesis from ketone bodies in rat brain. Evidence for conversion of acetoacetate into acetyl-coenzyme A in the cytosol.
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.
D000085:Acetates / Q000378:metabolism; D000090:Acetoacetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology; D003065:Coenzyme A / Q000031:analogs & derivatives*; D003600:Cytosol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008314:Malonates / Q000494:pharmacology; D051381:Rats; D014233:Tricarboxylic Acids / Q000494:pharmacology
D000085:Acetates; D000090:Acetoacetates; D002951:Citrates; D006885:Hydroxybutyrates; D008055:Lipids; D008314:Malonates; D014233:Tricarboxylic Acids; D000105:Acetyl Coenzyme A; D007930:Leucine; D005947:Glucose; D003065:Coenzyme A