ⓘ CYP2C9

                                     

ⓘ CYP2C9

CYP2C9 is an important cytochrome P450 enzyme with 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 data only for antifungal. Some 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as warfarin and phenytoin, and other routinely prescribed drugs such as acenocoumarol, tolbutamide, losartan, glipizide, and some nonsteroidal anti-inflammatory drugs. By contrast, the known extrahepatic CYP2C9 often metabolizes important endogenous compounds such as serotonin and, owing to its epoxygenase activity, various polyunsaturated fatty acids, converting these fatty acids to a wide range of biological active products.

In particular, arachidonic acid is metabolized by CYP2C9 to the next eicosatrienoic acid epoxide stereoisomer of eets sets: 5 P 6 Z-epoxy-8Z,11Z,14Z-eicosatetrienoic,5 s, 6 R-epoxy-8Z,11Z,14Z-eicosatetrienoic acid, 11 R,12 s-epoxy-8Z,11Z,14Z-eicosatetrienoic and 11 s,12 R-epoxy-5 DIGITS,8Z,14Z-eicosatetrienoic acids, and 14 R 15-epoxy-5 DIGITS,8Z,11Z-eicosatetrainoic and 14 of 15 R-epoxy-5 DIGITS,8Z,11Z-eicosatetrainoic acids. He also metablizes docosahexaenoic acid epoxydocosapentaenoic acids EDP in the first place, 19.20-epoxy isomers of eicosapentaenoic acid and eicosapentaenoic acid epoxyeicosatetraenoic acids EEQs in the first place 17.18-equalizer eeq and 14.15-function isomers. Animal models and a limited number of human studies implicate these epoxides in lowering hypertension, it protects from myocardial infarction and other insults to the heart, contributing to the growth and metastasis of certain cancers, inhibiting inflammation, stimulating the formation of blood vessels, and have different actions on the nervous tissue, including the modulation of neurohormone release, and blocking pain perception see epoxyeicosatrienoic acid epoxygenase.

In laboratory studies on human and animal cells and tissues and in vivo studies in animal models have shown that certain EEQs and edps is the action, which often oppose those of another product CYP450 enzymes, namely, 20-Hydroxyeicosatetraenoic acid 20-hete, mainly in the areas of adjustment of blood pressure, arterial thrombosis, and cancer growth. These studies also show that EPA and EEQs are: 1) more potent than Eets in reducing hypertension and pain perception, 2) more powerful than or equal to potency of eets in the suppression of inflammation, and 3) act oppositely from eets in that they inhibit angiogenesis, migration of endothelial cells, endothelial cell proliferation, and the growth and metastasis of human breast and prostate cancer cell lines, while Eets have a stimulating effect in each of these systems. Consumption of omega-3 fatty acid-rich diet dramatically increases serum and tissue levels of EEQs and edps in animals and man, and man is the most important change in the profile of PUFA metabolites, caused by biologically active omega-3 fatty acids.

CYP2C9 can also convert linoleic acid to potentially very toxic products, vernolic acid is also called leukotoxin and coronaric acid is also called isoleukotoxin, those of linoleic acid, epoxides cause multiple organ failure and acute respiratory distress in animals and may contribute to the development of these syndromes in humans.

                                     
  • Cytochrome P450 2 C 9 CYP2C9 a member of the CYP 2 C enzyme subfamily, ranks amongst the most important drug metabolizing enzymes in humans. Human CYP2C9 has been
  • Cytochrome P450 2 C 9 CYP2C9 a member of the CYP 2 C enzyme subfamily, ranks amongst the most important drug metabolizing enzymes in humans. Human CYP2C9 has been
  • epoxyeicosatetraenoic acids also termed EEQs Along with CYP 2 C 19, CYP 2 C 8, CYP2C9 CYP 2 J 2 and possibly CYP 2 S1 are the main producers of EETs and, very likely
  • epoxyeicosatetraenoic acids also termed EEQs Along with CYP 2 C 8, CYP2C9 CYP 2 C 19, CYP 2 J 2 and possibly CYP 2 S1 are the main producers of EETs and, very likely
  • epoxyeicosatetraenoic acids also termed EEQs While CYP 2 C 19, CYP 2 C 8, CYP2C9 CYP 2 J 2 and possibly CYP 2 S1 are the main producers of EETs and, very likely
  • Cytochrome P450 2 D6 CYP 2 D6 is an enzyme that in humans is encoded by the CYP 2 D6 gene. CYP 2 D6 is primarily expressed in the liver. It is also highly expressed
  • epoxyeicosatetraenoic acids also termed EEQs CYP 2 J 2 along with CYP 219, CYP 2 C 8, CYP2C9 and possibly CYP 2 S1 are the main producers of EETs and, very likely
  • Metabolism Transport Effects: Substrate of CYP 1A 2 minor CYP 2 B6 minor CYP2C9 minor CYP 2 E1 minor CYP 3A4 major P - glycoprotein ABCB1 Note: Assignment
  • e. DHA to epoxydocosapentaenoic acids i.e. EDPs CYP 2 C 8, CYP2C9 CYP 2 C 18, CYP 2 C 19, and CYP 2 J 2 metabolize endogenous PUFAs to signaling molecules: they
  • used as a probe for CYP 2 A6 activity. The CYP 2 A6 gene is part of a large cluster of cytochrome P450 genes from the CYP 2 A, CYP 2 B and CYP 2 F subfamilies on chromosome
  • Benzbromarone is a very potent inhibitor of CYP2C9 Several analogues of the drug have been developed as CYP2C9 and CYP 2 C 19 inhibitors for use in research. Benzbromarone