EFFECT OF PEROXISOMES PROLIFERATORS AND HYPOLIPEMIC AGENTS ON MITOCHONDRIAL INNER MEMBRANE LINKED D-3-HYDROXYBUTYRATE DEHYDROGENASE (BDH)

1/ D-3-hydroxybutyrate dehydrogenase EC 1.1.1.30 (BDH) activity was me asured in mitochondria of rats submitted to an intermittent feeding tr eatment 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 inh ibitory effect is abolished when the treatment is stopped and reappear s after a second treatment. 2/ Incubation of hypolipemic agents (cipro fibrate, clofibrate, clobuzarit, fenofibrate or 2,4 dichlorophenoxyace tic acid) with submitochondrial linked BDH leads to an inhibition in a concentration dependent manner. 3/ The protection by NAD(H) (coenzyme s) and by methyl-malonate (a substrate analogue and competitive inhibi tor) indicates that the inhibition occurs in the active site. On the o ther hand, there is a strong protection by phospholipid vesicles. This trapping effect may be attributed to lipophilic properties of hypolip emic agents. 4/ Comparative effect of hypolipemic agents on mitochondr ial BDH activity from rat liver and from Tetrahymena pyriformis indica tes the same inhibition and same protection effects. This supports con servation of the enzymatic properties according to the evolution.