Structural control of cytochrome P450-catalyzed ω-hydroxylation

Arch Biochem Biophys. 2011 Mar 1;507(1):86-94. doi: 10.1016/ Epub 2010 Aug 19.


The regiospecific or preferential ω-hydroxylation of hydrocarbon chains is thermodynamically disfavored because the ease of C-H bond hydroxylation depends on the bond strength, and the primary C-H bond of a terminal methyl group is stronger than the secondary or tertiary C-H bond adjacent to it. The hydroxylation reaction will therefore occur primarily at the adjacent secondary or tertiary C-H bond unless the protein structure specifically enforces primary C-H bond oxidation. Here we review the classes of enzymes that catalyze ω-hydroxylation and our current understanding of the structural features that promote the ω-hydroxylation of unbranched and methyl-branched hydrocarbon chains. The evidence indicates that steric constraints are used to favor reaction at the ω-site rather than at the more reactive (ω-1)-site.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bacteria / enzymology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Humans
  • Hydroxylation
  • Models, Molecular
  • Molecular Structure
  • Substrate Specificity


  • Bacterial Proteins
  • Fatty Acids
  • Cytochrome P-450 Enzyme System