Debrisoquine-type polymorphism of drug oxidation: purification from human liver of a cytochrome P450 isozyme with high activity for bufuralol hydroxylation

FEBS Lett. 1984 Aug 6;173(2):287-90. doi: 10.1016/0014-5793(84)80792-9.


Indirect evidence suggests that the genetically defective metabolism of drugs such as debrisoquine and bufuralol observed in up to 10% of the population (poor metabolizers) is caused by the absence or functional deficiency of a cytochrome P450 isozyme. Using bufuralol-1'-hydroxylation to carbinol to optimize the procedure, 3 cytochrome P450 isozymes (P450A, P450buf, P450C) were purified to apparent electrophoretic homogeneity from human liver microsomes. P450buf had a specific activity of 20.3 nmol carbinol X nmol P450-1 X 15 min-1 as compared to microsomes (10.0 nmol carbinol X nmol P450(-1) X 15 min-1) when (+)-bufuralol was used as substrate. The stereoselective metabolism of (-)- and (+)-bufuralol to carbinol by purified P450buf [(-)/(+) ratio: 0.13] was strikingly different from that in the microsomes of either an extensive [(-)/(+) ratio: 0.4] or poor metabolizer [(-)/(+) ratio: 0.83] of bufuralol. We propose that this isozyme is the major bufuralol and debrisoquine hydroxylating species and is the target of the genetic deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / metabolism*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / isolation & purification
  • Cytochrome P-450 Enzyme System / metabolism
  • Debrisoquin / metabolism*
  • Ethanolamines / metabolism*
  • Humans
  • Hydroxylation
  • Isoenzymes / genetics*
  • Isoenzymes / isolation & purification
  • Isoquinolines / metabolism*
  • Kinetics
  • Microsomes, Liver / metabolism*
  • Molecular Weight
  • Oxidation-Reduction
  • Polymorphism, Genetic*
  • Substrate Specificity


  • Adrenergic beta-Antagonists
  • Ethanolamines
  • Isoenzymes
  • Isoquinolines
  • bufuralol
  • Cytochrome P-450 Enzyme System
  • Debrisoquin