EFFECTERS OF THE MAMMALIAN PLASMA-MEMBRANE NADH-OXIDOREDUCTASE SYSTEM- SHORT-CHAIN UBIQUINONE ANALOGS AS POTENT STIMULATORS

In the presence of effecters variations in the two recognized activiti es of the plasma membrane NADH-oxidoreductase system were studied in s eparate, specific in vitro assays. We report here that ubiquinone anal ogues that contain a short, less hydrophobic side chain than coenzyme Q-10 dramatically stimulate the NADH-oxidase activity of isolated rat liver plasma membranes whereas they show no effect on the reductase ac tivity of isolated membranes. If measured in assays of the NADH:ferric yanide reductase of living cultured cells these compounds have only a limited effect; the oxidase activity of whole cells is not measurable in our hands. We have furthermore identified selective inhibitors of b oth enzyme activities. In particular, the NADH-oxidase activity can be significantly inhibited by structural analogues of ubiquinone, such a s capsaicin and resiniferatoxin. The NADH:ferricyanide reductase, on t he other hand, is particularly sensitive to pCMBS, indicating the pres ence of a sulfhydryl group or groups at its active site. The identific ation of these specific effecters of the different enzyme activities o f the PMOR yields further insights into the function of this system.