CYP2C subfamily

Miners, J. O. et al. (2000). Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes. Pharmacogenetics, 10, 267-70. 

Goldstein, J.A. (2001) Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. British Journal of Clinical Pharmacology, 52, 349-355. 

Metabolism of ramelteon consists primarily of oxidation to hydroxyl and carbonyl derivatives, with secondary metabolism producing glucuronide conjugates. CYP1A2 is the major isozyme involved in the hepatic metabolism of ramelteon the CYP2C subfamily and CYP3A4 isozymes also are involved to a minor degree. 

This is the most highly expressed member of the CYP2C subfamily in hepatic tissues. It is a polymorphic enzyme, and is involved in the metabolism of a number of anti-inflammatory drugs. 

The principal limitation of these data is the lack of definition of the individual forms for the CYP2C subfamily. Analysis of this subfamily has remained problematic due to high cross-reactivities of all of the distinct forms with most antibody preparations. In addition, Western blot analysis does not distinguish between active and inactive forms of the protein. Furthermore, distinct enzymes may have different affinities for coenzymes necessary for catalytic activity, which will serve to unlink abundance of the protein and its catalytic activity. Therefore the assumptions must be made that the ratios of active to inactive protein are similar for all forms and that all forms have similar affinities for coenzymes. These assumptions may not be justified. However, even with these limitations, the study of Shimada et al. (1994) contributes greatly to our understanding of relative enzyme abundance in human liver. In addition, the relative abundance data, coupled with the absolute P450 content (per unit protein) and the turnover numbers for enzyme-specific substrates (per unit protein), can provide an estimate of the turnover number for individual enzymes in the human liver membrane environment. This provides an important benchmark for evaluation of turnover number data from cDNA-expressed enzymes. 

Goldstein J, de Morals S. Biochemistry and molecular biologyof the human CYP2C subfamily. Pharmacogenetics 1994 4 285-299. 

CYP2C subfamily, responsible for the metabolism of 20% of the drugs on the market. It covers a wide variety of therapeutical classes. 

The overall prediction rate for the selective site of metabolism within the CYP2C subfamily based on the selective interaction profiling using the loading plots from a cPCA analysis based on flexible GRID interaction fields was 72.4%. 

Ikeda A, Hattori H, Odani A, Kimura J, Shibasaki H. Gynaecomastia in association with phenytoin and zonisa-mide in a patient having a CYP2C subfamily mutation. J Neurol Neurosurg Psychiatry 1998 65(5) 803. ... 

Ninomiya H, Mamiya K, Matsuo S, leiri I, Higuchi S, Tashiro N. Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Ther Drug Monit 2000 22(2) 230-2. 

Ohgiya, S., M. Komori, H. Ohi, K. Shiramatsu, N. Shinriki, and T. Kamataki (1992). Six-base deletion occurring in messages of human cytochrome P-450 in the CYP2C subfamily results in reduction of tolbutamide hydroxylase activity. Biochem. Int. 27, 1073-1081. 

Diclofenac has rapid absorption, extensive protein binding, and a short t (Table 26-2). There is a substantial first-pass effect, such that only -50% of diclofenac is available systemically. Diclofenac accumulates in synovial fluid after oral administration, which may explain why its duration of therapeutic effect is considerably longer than the plasma t - Diclofenac is metabolized in the liver by a member of the CYP2C subfamily to 4-hydroxydiclofenac, the principal metabolite, and other hydroxylated forms after glucuronidation and sulfation the metabolites are excreted in the urine (65%) and bile (35%). 

Lsoforms with paiticular reference to the CYP2C subfamily. Drug MeUtb. Dhp. 32, 333-339. 

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