Limited expression of functional cytochrome p450 2c subtypes in the liver and small intestine of domestic cats

Abstract

1. Compared to information for herbivores and omnivores, knowledge on xenobiotic metabolism in carnivores is limited. The cytochrome P450 2C (CYP2C) subfamily is recognized as one of the most important CYP groups in human and dog. We identified and characterized CYP2C isoforms and variants in cat, which is an obligate carnivore.

2. Quantitative RT-PCR and immunoblot analyses were carried out to evaluate the expression of CYP2C in the liver and small intestine. A functional CYP2C isoform was heterologously expressed in yeast microsomes to determine the enzymatic activity.

3. Cat had two CYP2C genes, 21 and 41, in the genome; however, CYP2C21P was a pseudogene that had many stop codons. Three splicing variants of CYP2C41 were identified (v1–v3), but only one of them (v1) showed a complete deduced amino acid sequence as CYP2C protein. Transcripts of feline CYP2C41v1 were detected but the amounts were negligible or very small in the liver and small intestine. Immunoreactivity to an antihuman CYP2C antibody was confirmed in the recombinant feline CYP2C41v1 but not in the feline liver.

4. Recombinant feline CYP2C41v1 metabolized several substrates, including dibenzylfluorescein that is specific to human CYP2C.

5. The results suggest a limited role of functional CYP2C isoforms in xenobiotic metabolism in cat.

Keywords:

• Carnivore
• cytochrome P450 2C
• domestic cats
• xenobiotics

Acknowledgments

We sincerely thank Dr. Isogai and Dr. Takahashi for providing animals and Ms. Tamura for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by Grants-in-Aid for Scientific Research (MEXT/JSPS KAKENHI 24580462 (C)) and a Grant-in-Aid to Cooperative Research from Rakuno Gakuen University (H.T.).