Vol. 28, Issue 4, 373-375, April 2000

SHORT COMMUNICATION
N-Methylprotoporphyrin Is a More Potent Inhibitor of Recombinant Human Than of Recombinant Chicken Ferrochelatase

Jeremy T. Gamble, Harry A. Dailey, and Gerald S. Marks

Department of Pharmacology and
Toxicology,Faculty of Health Sciences
Queen's University, Kingston, Ontario,
Canada (J.T.G., G.S.M.); and
Department of Microbiology,
Department of Biochemistry and
Molecular Biology
University of Georgia
Athens, Georgia (H.A.D.)

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 × 10³ nmol/mg protein, and with purified recombinant chicken FC was 2.07 × 10³ nmol/mg protein. The difference in EC₅₀ values 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 of N-methylPP. The second objective of this study was to compare the potency of N-methylPP between purified human and chicken FC. The EC₅₀ value of N-methylPP observed in the purified human FC preparation was 1.7 × 10⁶ nmol/mg protein (chicken FC 2.07 × 10³ nmol/mg protein). Thus, the potency of N-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.