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Gene Review:

CYP2C18 - cytochrome P450 2C21

Canis lupus familiaris

Synonyms: CYP2C19, CYP2C21, CYPIIC21

Blaisdell, J. et al., Shou, M. et al., Lu, P. et al., Kuroha, M. et al., Graham, M.J. et al., et al.

Shou, Norcross, Sandig, Lu, Li, Lin, Mei, Rodrigues, Rushmore, Paulson, Engel, Reitz, Bolten, Burton, Maziasz, Yan, Schoenhard,

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High impact information on CYP2C21

Their selectivity was evaluated using phenacetin O-deethylation (CYP1A), diazepam (DZ) N1-demethylation (CYP2B11), diclofenac 4'-hydrxylation (CYP2C21), bufuralol 1'-hydroxylation (CYP2D11), and DZ C3-hydroxylation (CYP3A12) activities in dog liver microsomes (DLM) [1].
However, the 16alpha-hydroxylation of testosterone was catalyzed by CYP2C21 also (Km = 6.4 microM for CYP2C21) [2].
CYP2C21 was also capable of catalyzing diclofenac 4'-hydroxylation, although some activity was detected with CYP2B11 [2].
Canine CYP2C41 is more homologous to the human CYP2Cs than CYP2C21 [3].
Furthermore, no influence of KTZ on the pharmacokinetics of CYP1A1/2, CYP2C21, and CYP2D15 substrates are likely [4].

Biological context of CYP2C21

Two members of the canine cytochrome P4502C subfamily [CYP2C21 and CYP2C41 (sequence has been submitted to Genbank with accession number AF016248)] were cloned from three beagle liver cDNA libraries [3].
6. All dog livers expressed mRNA and CYP3A12, CYP2B11, CYP2C21 proteins, with no sex differences being found [5].

Associations of CYP2C21 with chemical compounds

Therefore, the 6beta- and 16alpha-hydroxylation of testosterone can potentially be employed as markers of CYP3A12 and CYP2C21 (at low concentration), respectively [2].
Canine rCYP2D15 and its variants, but not CYP2B11, CYP2C21, and CYP3A12, readily metabolized celecoxib [6].

Analytical, diagnostic and therapeutic context of CYP2C21

Reverse transcription-polymerase chain reaction-based restriction enzyme tests for CYP2C21 and 2C41 mRNAs as well as polymerase chain reaction-based tests for genomic DNA were developed [3].

References

Selective inhibition of dog hepatic CYP2B11 and CYP3A12. Lu, P., Singh, S.B., Carr, B.A., Fang, Y., Xiang, C.D., Rushmore, T.H., Rodrigues, A.D., Shou, M. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
Substrate specificity and kinetic properties of seven heterologously expressed dog cytochromes p450. Shou, M., Norcross, R., Sandig, G., Lu, P., Li, Y., Lin, Y., Mei, Q., Rodrigues, A.D., Rushmore, T.H. Drug Metab. Dispos. (2003) [Pubmed]
Isolation of a new canine cytochrome P450 CDNA from the cytochrome P450 2C subfamily (CYP2C41) and evidence for polymorphic differences in its expression. Blaisdell, J., Goldstein, J.A., Bai, S.A. Drug Metab. Dispos. (1998) [Pubmed]
In vitro characterization of the inhibitory effects of ketoconazole on metabolic activities of cytochrome P-450 in canine hepatic microsomes. Kuroha, M., Kuze, Y., Shimoda, M., Kokue, E. Am. J. Vet. Res. (2002) [Pubmed]
mRNA and protein expression of dog liver cytochromes P450 in relation to the metabolism of human CYP2C substrates. Graham, M.J., Bell, A.R., Crewe, H.K., Moorcraft, C.L., Walker, L., Whittaker, E.F., Lennard, M.S. Xenobiotica (2003) [Pubmed]
Evidence for polymorphism in the canine metabolism of the cyclooxygenase 2 inhibitor, celecoxib. Paulson, S.K., Engel, L., Reitz, B., Bolten, S., Burton, E.G., Maziasz, T.J., Yan, B., Schoenhard, G.L. Drug Metab. Dispos. (1999) [Pubmed]

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CYP2C19	Bos taurus
LOC522146	Bos taurus
LOC785540	Bos taurus
CYP2C19	Homo sapiens
CYP2C75	Macaca mulatta
LOC740956	Pan troglodytes
Cyp2c6v1	Rattus norvegicus

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