INHIBITION OF MAMMALIAN PROTOPORPHYRINOGEN OXIDASE BY ACIFLUORFEN

We have studied the kinetics of the inhibition of mitochondrial protop orphyrinogen oxidase (PPO) from liver and placenta of 3 mammalian spec ies by the diphenyl ether herbicide acifluorfen (AF). AF competitively inhibited PPO from human liver and placenta, mouse liver and pig plac enta with respect to its substrate protoporphyrinogen. In contrast, mi xed-type inhibition was shown for pig liver. The differing results sho wn in pig liver may point to structural differences in PPO derived fro m different species and tissues. We have also compared the effects of AF on the function of PPO in human lymphoblasts from normal subjects a nd those with variegate porphyria, an inherited disorder of PPO. Compe titive inhibition was shown for both and there were no significant dif ferences in the values of K-s or K-i.