Oxygen-18 Labeling Reveals a Mixed Fe-O Mechanism in the Last Step of Cytochrome P450 51 Sterol 14α-Demethylation.

ABSTRACT: The 14α-demethylation step is critical in eukaryotic sterol biosynthesis, catalyzed by cytochrome P450 (P450) Family 51 enzymes, for example, with lanosterol in mammals. This conserved three-step reaction terminates in a C-C cleavage step that generates formic acid, the nature of which has been controversial. Proposed mechanisms involve roles of P450 Compound 0 (ferric peroxide anion, FeO₂ ^- ) or Compound I (perferryl oxygen, FeO³⁺ ) reacting with either the aldehyde or its hydrate, respectively. Analysis of ¹⁸ O incorporation into formic acid from ¹⁸ O₂ provides a means of distinguishing the two mechanisms. Human P450 51A1 incorporated 88 % ¹⁸ O (one atom) into formic acid, consistent with a major but not exclusi

SUBMITTER: McCarty KD 

PROVIDER: S-EPMC11494732 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature