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.