Abstract

The potency of N-methylprotoporphyrin IX (N-methylPP) as a ferrochelatase (FC) inhibitor has been previously studied using crude chick embryo liver FC preparations. However, interactions between N-methylprotoporphyrin IX (N-methylPP) and impurities in the enzyme preparation may have compromised the results. The first objective of this study was to compare the potency of N-methylPP as an inhibitor of purified chicken FC and crude chick embryo liver FC. The EC₅₀ values of N-methylPP previously observed in crude chick embryo liver FC was 2.9 × 10⁻³nmol/mg protein, and with purified recombinant chicken FC was 2.07 × 10⁻³ nmol/mg protein. The difference in EC₅₀values was not statistically significant, and we conclude that interactions between N-methylPP and impurities in crude enzyme preparations did not affect the estimation of potency ofN-methylPP. The second objective of this study was to compare the potency of N-methylPP between purified human and chicken FC. The EC₅₀ value ofN-methylPP observed in the purified human FC preparation was 1.7 × 10⁻⁶ nmol/mg protein (chicken FC 2.07 × 10⁻³ nmol/mg protein). Thus, the potency ofN-methylPP was much higher with purified human FC than with purified chicken FC. Because the porphyrinogenicity of several xenobiotics involves N-alkylprotoporphyrin IX formation, results on drug-induced porphyria obtained with avian species may underestimate the potential porphyrinogenicity in humans.