RT Journal Article
SR Electronic
T1 <em>N</em>-Methylprotoporphyrin Is a More Potent Inhibitor of Recombinant Human Than of Recombinant Chicken Ferrochelatase
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 373
OP 375
VO 28
IS 4
A1 Jeremy T. Gamble
A1 Harry A. Dailey
A1 Gerald S. Marks
YR 2000
UL http://dmd.aspetjournals.org/content/28/4/373.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics