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.

Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure

“…Glucuronidation deficiency for phase II metabolism is well known in cats, but the study on CYPs, particularly CYP1-CYP3 families, has not extensively been clarified. Several studies have reported the genetic polymorphisms, metabolic activities, and protein and mRNA expressions of some feline CYPs, that is, CYP1A, CYP2A, CYP2B, CYP2C, CYP2D, CYP2E, and CYP3A, have been reported (Honda et al, 2011;Komatsu et al, 2010;Okamatsu et al, 2017a;Ono et al, 2019;Shah et al, 2007;Sugiyama et al, 2019;Tanaka et al, 2006), and most of these reviewed in the liver. However, the CYP expression is also found in extrahepatic tissues.…”

Comparative analysis of the effect of PO administered acid suppressants on gastric pH in healthy cats

“…The S‐omeprazole is less sensitive to metabolism by Cytochrome P450 2C19 (CYP2C19) compared to R‐omeprazole, and maintains better drug plasma concentrations in people 19 . However, the role of CYP2C in xenobiotic metabolism in cats recently has been questioned because researchers identified negligible to no functional CYP2C hepatic protein in cats and suggested that CYP2C does not play a major role in the systemic clearance of any xenobiotics in cat 20 . Therefore, additional comparative pharmacodynamic studies in the same cohort of cats are needed before definitive conclusions can be drawn regarding the superiority of esomeprazole over omeprazole in cats.…”

The profile of urinary lipid metabolites in cats

“…Ono. Y et al , also reported the low activation of another major CYP isoform CYP2C in liver of cat [ 16 ]. These features may be responsible for the low detection number of CYP metabolites in healthy cat urine.…”