Adriamycin as an inhibitor of 11 beta-hydroxylase activity in adrenal cortex mitochondria.
Inhibition of 11 beta-hydroxylase activity was observed to be due to the interaction of adriamycin with adrenal cortex mitochondria. The inhibition of the enzyme was uncompetitive, with an apparent Ki of 100 microM, and was dependent upon the concentration of the drug and the time of incubation. Adriamycin increased the oxygen consumption of these mitochondria. EPR studies showed that adriamycin was reduced to a free radical semiquinone which served to shuttle electrons to oxygen, leading to an impairment in the reduction of cytochrome P450. It is suggested this may be the mechanism for the inhibitory effect of the drug on 11 beta-hydroxylase activity.
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D010101:Oxygen Consumption / Q000187:drug effects; D013053:Spectrophotometry; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors*; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*
D004317:Doxorubicin; D013250:Steroid Hydroxylases; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone