Summary
NADH oxidase was markedly inhibited by dilute antimitochondrial antibody in the presence of a serum factor found in man, guinea pigs and rabbits. Little or no inhibition occurred when the additional serum was from mice or was treated with ammonia, EDTA, zymosan, or immune precipitates, or was heated to 56°C for 30 min. The factor which potentiates enzyme inhibition by antibody thus has all the properties of the hemolytic complement system.
NADH-cytochrome C reductase, succinate-cytochrome C reductase, and cytochrome oxidase were markedly inhibited by the antimitochondrial serum. This inhibitory effect was overcome on addition of a complement source.
Addition of small amounts of cytochrome C to the NADH oxidase system reversed the inhibitory effect of complement in the presence of antibody. Added cytochrome C did not serve as a terminal “trap” for electrons.
These observations are consistent with the interpretation that antibody alone blocks access sites for the oxidation and reduction of exogenous substrate cytochrome C, while sparing the endogenous enzymatically functioning hemeprotein. On addition of complement, however, binding sites for exogenous cytochrome C are “revealed”, whereas endogenous cytochrome C is inactivated. This suggests specific effects of complement on the binding sites for cytochrome C. These effects of complement are analogous to the action of certain detergents and snake venom phospholipase A on electron transport particles, except that cytochrome C could not be recovered in the supernatant solutions.
Footnotes
Supported by U. S. Public Health Service Grant AM-03421, Rheumatic Disease Training Grant 2A-5233, and the Parke-Davis Company, Detroit, Michigan.
