Cytochrome P450 2C9 is abbreviated CYP2C9 is an enzyme that in humans is encoded by the CYP2C9 gene.



Chromosome 10 



CYP2C9 is an important cytochrome P450 enzyme, which plays a major role in the oxidation of both xenobiotic and endogenous compounds. 



CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes. 



Some 100 therapeutic drugs are metabolized by CYP2C9: warfarin and phenytoin, acenocoumarol, tolbutamide, losartan, glipizide, and some nonsteroidal anti-inflammatory drugs. 



The extrahepatic CYP2C9 often metabolizes important endogenous compounds such as serotonin, and polyunsaturated fatty acids, converting  polyunsaturated fatty acids, to biological active products.



CYP2C9 metabolizes arachidonic acid, associated with reducing hypertension, protecting against myocardial infarction,  promoting the growth and metastasis of certain cancers, inhibiting inflammation,stimulating blood vessel formation, and modulating neurohormone release and blocking pain perception.



CYP2C9 may also metabolize linoleic acid to the potentially very toxic products.



Genetic variants exist in CYP2C9 expression because 



The CYP2C9 gene is highly polymorphic., with more than 50 single nucleotide polymorphisms (SNPs) have been described in the regulatory and coding regions of the CYP2C9 gene.



Some of these single nucleotide polymorphisms  have altered enzyme activity compared with wild type.



Mutant CYP2C9 genotypes are associated with significant reduction of in metabolism and daily dose requirements of selected CYP2C9 substrate. 



Diminished metabolic capacity because of genetic polymorphisms or drug-drug interactions can lead to toxicity at normal therapeutic doses of warfarin and phenytoin.



CYP2C9*1 is assigned to normal enzyme function (wild-type). 



The two most well-characterized variant alleles are CYP2C9*2 and CYP2C9*3, causing reductions in enzyme activity of 30% and 80%, respectively.



The carriers of homozygote CYP2C9*1, are extensive or normal metabolizers (EM). 



The carriers of the CYP2C9*2 and CYP2C9*3 alleles in a heterozygous state are designated intermediate metabolizers.



Individuals carrying two of these alleles-


*2/*3, *2/*2  are poor metabolizers.



In patients with wild-type alleles (*1/*1), concluded that the mean warfarin maintenance dose was 92% in *1/*2, 74% in *1/*3, 63% in *2/*3, 61% in *2/*2 and 34% in 3/*3 alleles.



The T allele at rs7089580 is associated with increased CYP2C9 gene expression which leads to increased rate of warfarin metabolism and increased warfarin dose requirements. 



Most inhibitors of CYP2C9 are competitive inhibitors. 



Noncompetitive inhibitors of CYP2C9 include nifedipine.



Inhibitors of CYP2C9 can be classified by their potency, such as:



Strong with at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.



Moderate with at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.



Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.




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