Effect of (-)hydroxycitrate on the activities of ATP citrate lyase and the enzymes of acetyl-CoA metabolism in rat brain.
1. (-)Hyrdoxycitrate is a potent inhibitor of ATP citrate (pro-3S)lyase (EC 4.1.3.8) from rat brain, the inhibition being uncompetitive with respect to MgATP2-and competitive with citrate (Ki 0.8 muM). 2. The rate of oxygen consumption by rat brain synaptosomes and the activities of fatty acid synthetase, carnitine acetyltransferase, glucose-6-phosphate dehydrogenase and acetyl-CoA-synthetase are not affected by (-)hydroxycitrate. 3. (-)Hydroxycitrate inhibits the activities of isocitrate dehydrogenase, malate dehydrogenase (decarboxylating) and aconitate hydratase at millimolar concentrations.
D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors*; D000109:Acetylcholine / Q000096:biosynthesis; D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology*; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D007521:Isocitrate Dehydrogenase / Q000037:antagonists & inhibitors; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D008297:Male; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002951:Citrates; D005227:Fatty Acids; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D001275:ATP Citrate (pro-S)-Lyase; D007652:Oxo-Acid-Lyases; D000154:Aconitate Hydratase; D000109:Acetylcholine