Positional specificity of rabbit CYP4B1 for omega-hydroxylation1 of short-medium chain fatty acids and hydrocarbons

Biochem Biophys Res Commun. 1998 Jul 20;248(2):352-5. doi: 10.1006/bbrc.1998.8842.


Rabbit CYP4B1 was incubated with a series of fatty acid and hydrocarbon substrates and metabolites were identified by gas chromatography and gas chromatography/mass spectrometry. C-7 to C-10 n-alkyl fatty acids were preferentially hydroxylated at the terminal carbon (omega/omega-1 = 1.1-7.4) with turnover numbers of 1-11 min-1. The C-7 to C-10 n-alkyl hydrocarbons exhibited turnover numbers of 11-33 min-1 for the corresponding reactions and even higher regioselectivities for hydroxylation at the thermodynamically disfavored site (omega/omega-1 = 1.6-23). These results demonstrate a functional link between CYP4B1 and other CYP4 fatty acid hydroxylases, and show further that CYP4B1's unusual positional specificity is not dictated by the presence of a carboxylate (or polar) anchor on the substrate. This suggests the presence of a dominant hydrocarbon binding site which effectively restricts the access of short-medium chain n-alkyl substrates to the perferryl species in the active site of rabbit CYP4B1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Binding Sites / physiology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Fatty Acids / chemistry*
  • Hydroxylation
  • Kinetics
  • Mixed Function Oxygenases / metabolism
  • Rabbits
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Thermodynamics
  • Xenobiotics / metabolism


  • Fatty Acids
  • Recombinant Proteins
  • Xenobiotics
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • cytochrome P-450 CYP4B1