Chicken cytochrome P450 1A5 is the key enzyme for metabolizing T-2 toxin to 3'OH-T-2

Int J Mol Sci. 2013 May 23;14(6):10809-18. doi: 10.3390/ijms140610809.

Abstract

The transmission of T-2 toxin and its metabolites into the edible tissues of poultry has potential effects on human health. We report that T-2 toxin significantly induces CYP1A4 and CYP1A5 expression in chicken embryonic hepatocyte cells. The enzyme activity assays of CYP1A4 and CYP1A5 heterologously expressed in HeLa cells indicate that only CYP1A5 metabolizes T-2 to 3'OH-T-2 by the 3'-hydroxylation of isovaleryl groups. In vitro enzyme assays of recombinant CYP1A5 expressed in DH5α further confirm that CYP1A5 can convert T-2 into TC-1 (3'OH-T-2). Therefore, CYP1A5 is critical for the metabolism of trichothecene mycotoxin in chickens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Biocatalysis
  • Chickens / metabolism*
  • Chromatography, Liquid
  • HeLa Cells
  • Humans
  • Inactivation, Metabolic*
  • Protein Structure, Secondary
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Spectrometry, Mass, Electrospray Ionization
  • T-2 Toxin / analogs & derivatives*
  • T-2 Toxin / chemistry
  • T-2 Toxin / metabolism

Substances

  • Recombinant Proteins
  • 3'-hydroxy-T-2 toxin
  • Aryl Hydrocarbon Hydroxylases
  • cytochrome P-450 CYP1A5
  • T-2 Toxin