Purification and characterization of human liver cytochrome P-450-ALC

Biochem Biophys Res Commun. 1987 Oct 14;148(1):232-8. doi: 10.1016/0006-291x(87)91100-4.

Abstract

Cytochrome P-450-ALC, an ethanol-oxidizing form of microsomal cytochrome P-450 (P-450), has been purified from human liver. P-450-ALC (Mr = 54,000 daltons) is a low-spin ferric hemeprotein with a CO-reduced Soret maximum at 452 nm, and has an NH2-terminal amino acid sequence nearly identical to that deduced from a human P-450-ALC cDNA clone. In a reconstituted system, P-450-ALC oxidizes ethanol and aniline at turnover rates (12.2 and 7.3 nmol min-1, respectively) 10-fold greater than two other human P-450 isozymes (termed P-450-B and P-450-C) purified from the same liver. Both P-450-ALC and P-450-C effectively demethylate N-nitrosodimethylamine (NDMA) at low substrate concentrations (0.5 mM), especially in the presence of cytochrome b5. Our results provide direct evidence for a liver P-450 isozyme in humans with catalytic properties similar to the related alcohol-inducible rodent P-450s and also reveal a new human NDMA demethylase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / isolation & purification*
  • Cytochrome P-450 Enzyme System / metabolism
  • Ethanol / metabolism*
  • Humans
  • Microsomes, Liver / metabolism*
  • Molecular Sequence Data
  • Molecular Weight
  • Sequence Homology, Nucleic Acid
  • Substrate Specificity

Substances

  • Ethanol
  • Cytochrome P-450 Enzyme System