Functional characterization of CYP2A13 polymorphisms

K. E. Schlicht, N. Michno, B. D. Smith, E. E. Scott, Sharon E Murphy

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


CYP2A13 is an efficient catalyst of metabolic activation of the human carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN). This study investigated the functional consequences of CYP2A13 polymorphisms that result in single amino acid substitutions. Five CYP2A13 variants, namely CYP2A13*2 (R257C), CYP2A13*5 (F453Y), CYP2A13*6 (R494C), CYP2A13*8 (D158E), and CYP2A13*9 (V323L), were expressed and evaluated for coumarin binding affinity, coumarin 7-hydroxylation, and α-hydroxylation of (S)-NNN and NNK. In addition, the 133_134 Thr deletion variant, coded for by CYP2A13*3, was expressed but was not stable to the protein purification procedure. A 30-42% decrease in coumarin 7-hydroxylation catalytic efficiency was determined for R257C and D158E. No effect on coumarin binding or (S)-NNN metabolism was observed. Three variants, R257C, D158E, and V323L, had two- to threefold decreased catalytic efficiency for NNK α-hydroxylation. CYP2A13 polymorphisms resulted in modest changes in coumarin 7-hydroxylation and NNK α-hydroxylation activities in vitro. Although these changes are not likely to impact in vivo metabolism, these data should aid in the interpretation and design of future epidemiology studies.

Original languageEnglish (US)
Pages (from-to)1439-1449
Number of pages11
Issue number12
StatePublished - Dec 2007


  • 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK)
  • CYP2A13
  • Coumarin
  • Cytochrome P450 (CYP)
  • N′-nitrosonornicotine (NNN)

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