SURAMIN - AN INHIBITOR OF THE FINAL STEPS OF THE MINERALOCORTICOID PATHWAY

The authors used incubated adrenal mitochondria to study the in vitro effect of suramin, an antiparasitic drug, on the transformation of cor ticosterone and 18-hydroxycorticosterone into aldosterone. The results show that, under conditions preserving membrane integrity, the ''impe rmeance'' of suramin meant that concentrations similar to the plasma-l evels reached in treated patients induced only slight inhibition of th e final intramitochondrial steps in aldosterone synthesis. However, su ramin strongly inhibited mitochondrial respiration. The inhibition of two intramitochondrial mechanisms (respiration and steroid synthesis) suggests that the effect of suramin involves partial inhibition of met abolic intermediate carriers. The inhibition of the activity of variou s extramitochondrial enzymes involved in intermediate metabolism, sugg ests that the inhibition of steroid biosynthesis can be explained only on the basis of an extramitochondrial action of suramin. The action o f suramin must, therefore, primarily and directly affect extramitochon drial steroid synthesis and only indirectly affect intramitochondrial steroid synthesis as a result of an impact on the reducing equivalent supply. However, even if suramin does not bind to cytochrome P450 11be ta which catalyzes the final steps of aldosterone biosynthesis pathway , this does not imply that suramin has no direct effect on steroid syn thesis within the mitochondria, in addition to its toxic effects, part icularly if the cell structure is disrupted (as is often the case in t umor tissues).