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 lownanomolar binding constants, andmuch poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts alltrans retinoic acid (atRA) to 4-hydroxy atRA and all-Trans retinol to 4-OH all-Trans retinol, and it also oxidizes retinal. The enzyme much less efficiently oxidizes 17b-estradiol to 2-hydroxy-(17b)-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 771-780 |
| Number of pages | 10 |
| Journal | Drug Metabolism and Disposition |
| Volume | 44 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2016 |
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ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
Cite this
Catalytic activities of tumor-specific human cytochrome P450 CYP2W1 toward endogenous substrates. / Zhao, Yan; Wan, Debin; Yang, Jun; Hammock, Bruce D.; De Montellano, Paul R Ortiz.
In: Drug Metabolism and Disposition, Vol. 44, No. 5, 2016, p. 771-780.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Catalytic activities of tumor-specific human cytochrome P450 CYP2W1 toward endogenous substrates
AU - Zhao, Yan
AU - Wan, Debin
AU - Yang, Jun
AU - Hammock, Bruce D.
AU - De Montellano, Paul R Ortiz
PY - 2016
Y1 - 2016
N2 - 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 lownanomolar binding constants, andmuch poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts alltrans retinoic acid (atRA) to 4-hydroxy atRA and all-Trans retinol to 4-OH all-Trans retinol, and it also oxidizes retinal. The enzyme much less efficiently oxidizes 17b-estradiol to 2-hydroxy-(17b)-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.
AB - 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 lownanomolar binding constants, andmuch poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts alltrans retinoic acid (atRA) to 4-hydroxy atRA and all-Trans retinol to 4-OH all-Trans retinol, and it also oxidizes retinal. The enzyme much less efficiently oxidizes 17b-estradiol to 2-hydroxy-(17b)-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.
UR - http://www.scopus.com/inward/record.url?scp=85011410547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011410547&partnerID=8YFLogxK
U2 - 10.1124/dmd.116.069633
DO - 10.1124/dmd.116.069633
M3 - Article
C2 - 26936974
AN - SCOPUS:85011410547
VL - 44
SP - 771
EP - 780
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 5
ER -