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Theoretical Chemistry Accounts

, Volume 121, Issue 5–6, pp 313–319 | Cite as

Regioselectivity preference of testosterone hydroxylation by cytochrome P450 3A4

  • Yan Zhang
  • Phani Morisetti
  • Jeffery Kim
  • Lynelle Smith
  • Hai LinEmail author
Regular Article

Abstract

Theoretical studies are presented into the experimentally observed regioselectivity difference of testosterone hydroxylation by cytochrome P450 3A4 at the 1β, 2β, 6β, and 15β positions. Such regioselectivity is investigated by density functional theory calculations on a model system. The barrier heights of hydrogen abstraction, which are corrected by zero-point vibrational energies, are computed to be about 10.1, 13.6, 14.4, and 16.2 kcal/mol for the 6β-, 2β-, 15β-, and 1β-positions, respectively. The calculated barriers suggest the regioselectivity preference of 6β ≫ 2β > 15β > 1β, which is in good agreement with experimental findings.

Keywords

Cytochrome P450 3A4 Testosterone hydroxylation Regioselectivity Density functional theory 

Notes

Acknowledgments

This research is supported by the Research Corporation. We thank the National Cancer Institute-Frederick Advanced Biomedical Computing Center for providing CPU time and access to the Gaussian03 program. We thank Dr. Hoyt Meyer for critically reading the manuscript.

Supplementary material

214_2008_480_MOESM1_ESM.pdf (440 kb)
MOESM1 (PDF 439 kb)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Yan Zhang
    • 1
  • Phani Morisetti
    • 1
  • Jeffery Kim
    • 1
    • 2
  • Lynelle Smith
    • 1
  • Hai Lin
    • 1
    Email author
  1. 1.Chemistry DepartmentUniversity of Colorado DenverDenverUSA
  2. 2.Rush University Medical CollegeChicagoUSA

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