Comparison of the effects of 2-chloropropionate and dichloroacetate on ketogenesis and lipogenesis in isolated rat hepatocytes.
The respective effects of 2-chloropropionate and dichloroacetate on the pyruvate metabolic crossroads, lipogenesis and ketogenesis, were compared in hepatocytes isolated from fed rats. 2-Chloropropionate acts as an exclusive pyruvate dehydrogenase activator: it increases ketogenesis, lipogenesis, Krebs cycle intermediates and mitochondrial NADH/NAD+ ratio. The effects of dichloroacetate depend on experimental conditions and the intensity of its catabolization into oxalate: the resultant action of dichloroacetate on tested parameters combines the effects of pyruvate dehydrogenase activation on the one hand, and pyruvate carboxylase inhibition by oxalate on the other. A mixture of 2-chloropropionate plus oxalate mimics the effects of dichloroacetate. In hepatocytes from fed rats, endogenous lipogenesis is correlated with the mitochondrial NADH/NAD+ ratio, irrespective of the effector added.
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004347:Drug Interactions; D006843:Hydrocarbons, Chlorinated; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis; D007659:Ketones / Q000096:biosynthesis*; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010070:Oxalates / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D006843:Hydrocarbons, Chlorinated; D007657:Ketone Bodies; D007659:Ketones; D008055:Lipids; D010070:Oxalates; D011422:Propionates; D011773:Pyruvates; D003999:Dichloroacetic Acid; C021974:2-chloropropionic acid