Contributions of cytosolic and mitochondrial acetyl-CoA syntheses to the activation of lipogenic acetate in rat liver.
Acetate derived from ethanol oxidation is activated by cytosolic and mitochondrial acetyl-CoA synthetases before contributing to the extra-mitochondrial processes of fatty acid and 3-beta-hydroxysterol synthesis. Mitochondrially-generated acetyl-CoA is transferred to the cytosol via citrate and ATP-citrate lyase; this transfer is blocked by (-)-hydroxycitrate. Rats were injected IV with 3.3 mmol/kg of [2-3H,2-14C] acetate and IP with either 0.5 mmol/kg hydroxycitrate or saline. After one hour, the rats were killed and the incorporation of label was measured in liver fatty acids and 3-beta-hydroxysterols. The 3H/14C ratio was increased by 12 and 13% in the fatty acids and 3-beta-hydroxysterols of the hydroxycitrate-treated group. The lower ratio in the fatty acids and 3-beta-hydroxysterols derived from mitochondrially-generated acetyl-CoA is ascribed to a loss of 3H in the citrate synthase reaction. The data showed that (1) fatty acids and 3-beta-hydroxysterols syntheses use the same pool of cytosolic acetyl-CoA; and (2) in the absence of an isotope effect in the citrate synthase reaction, mitochondrially-generated acetyl-CoA contributes about 36% to lipogenesis from acetate.
D000106:Acetate-CoA Ligase / Q000378:metabolism*; D000085:Acetates / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D003066:Coenzyme A Ligases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats; D013261:Sterols / Q000096:biosynthesis
D000085:Acetates; D005227:Fatty Acids; D013261:Sterols; D003066:Coenzyme A Ligases; D000106:Acetate-CoA Ligase