Effect of peroxisomes proliferators and hypolipemic agents on mitochondrial inner membrane linked D-3-hydroxybutyrate...

1. D-3-hydroxybutyrate dehydrogenase EC 1.1.1.30 (BDH) activity was measured in mitochondria of rats submitted to an intermittent feeding treatment with ciprofibrate or fenofibrate, i.e. fibrate analogues with hypolipemic activity and peroxisome proliferation properties. Our data shows an inhibition of rat liver mitochondrial BDH activity. This inhibitory effect is abolished when the treatment is stopped and reappears after a second treatment. 2. Incubation of hypolipemic agents (ciprofibrate, clofibrate, clobuzarit, fenofibrate or 2,4 dichlorophenoxyacetic acid) with submitochondrial linked BDH leads to an inhibition in a concentration dependent manner. 3. The protection by NAD(H) (coenzymes) and by methyl-malonate (a substrate analogue and competitive inhibitor) indicates that the inhibition occurs in the active site. On the other hand, there is a strong protection by phospholipid vesicles. This trapping effect may be attributed to lipophilic properties of hypolipemic agents. 4. Comparative effect of hypolipemic agents on mitochondrial BDH activity from rat liver and from Tetrahymena pyriformis indicates the same inhibition and same protection effects. This supports conservation of the enzymatic properties according to the evolution.