Effect of a heme-peptide derived from cytochrome-c on lipid peroxidation. II. Experiments with liver microsomes.

ADP-Fe2+ stimulated, NADPH dependent lipid peroxidation of liver microsomes (as measured by malondialdehyde formation) was not inhibited by c-heme-nonapeptide, unlike the same process in brain microsomes. However, in the presence of 5 mM aminopyrine (causing partial inhibition) or SKF-525A (a specific inhibitor of cytochrome P450) the residual activity of lipid peroxidation of liver microsomes was markedly inhibited by c-heme-nonapeptide. Further, c-heme-nonapeptide itself prevented the transient accumulation of lipid hydroperoxides during ADP-Fe2+ stimulated lipid peroxidation. These results led us to suggest two different pathways of lipid peroxidation. The first route involves cytochrome P450. The second pathway, which can be inhibited by c-heme-nonapeptide, appears to be more important physiologically.