2. Academic Validation
  3. Catalytic Activities of Tumor-Specific Human Cytochrome P450 CYP2W1 Toward Endogenous Substrates

Catalytic Activities of Tumor-Specific Human Cytochrome P450 CYP2W1 Toward Endogenous Substrates

  • Drug Metab Dispos. 2016 May;44(5):771-80. doi: 10.1124/dmd.116.069633.
Yan Zhao 1,  Debin Wan 1,  Jun Yang 1,  Bruce D Hammock 1,  Paul R Ortiz de Montellano 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.).
  • 2 Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.) Ortiz@cgl.ucsf.edu.
PMID: 26936974 DOI: 10.1124/dmd.116.069633
Abstract

CYP2W1 is a recently discovered human Cytochrome P450 enzyme with a distinctive tumor-specific expression pattern. We show here that CYP2W1 exhibits tight binding affinities for retinoids, which have low nanomolar binding constants, and much poorer binding constants in the micromolar range for four Other ligands. CYP2W1 converts all-transretinoic acid (atRA) to 4-hydroxyatRA and all-transretinol to 4-OH all-transretinol, and it also oxidizes retinal. The Enzyme much less efficiently oxidizes 17β-estradiol to 2-hydroxy-(17β)-estradiol and farnesol to a monohydroxylated product; arachidonic acid is, at best, a negligible substrate. These findings indicate that CYP2W1 probably plays an important role in localized retinoid metabolism that may be intimately linked to its involvement in tumor development.

Figures