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CYP4F8
Cytochrome P450 4F8 is a protein that in humans is encoded by the ''CYP4F8'' gene. Function This gene, CYP4F8, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and functions as a 19-hydroxylase of the arachidonic acid metabolite, prostaglandin H2 (PGH2) and the Dihomo-γ-linolenic acid metabolite PGH1 in seminal vesicles. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is approximately 18 kb away. In addition to seminal vesicles, CYP4F8 is expressed in kidney, prostate, epidermis, and corneal epithelium, and its mRNA has been found in retina; CYP4F8 is also greatly up-regulated in psoriatic skin. In addition to its ability to metabolize and presumably thereby to inactivate or reduce the ac ...
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CYP4F12
Cytochrome P450 4F12 is a protein that, in humans, is encoded by the ''CYP4F12'' gene. Gene family The ''CYP4F12'' gene encodes a member of the cytochrome P450 superfamily of enzymes. It is located within a cluster of P450 genes on chromosome 19. Cytochrome P450 proteins are monooxygenases that catalyze a wide array of reactions involved in drug metabolism and in the synthesis of cholesterol, steroids, and other lipids. Expression and localization CYP4F12 is thought to localize to the endoplasmic reticulum. It is expressed in the liver and throughout the gastrointestinal tract. The enzyme is known to metabolize the antihistamines ebastine and terfenadine, suggesting it may play a role in the metabolism of these and other drugs. Substrate specificity When expressed in yeast, CYP4F12 oxidizes arachidonic acid by hydroxylating carbon 18 or 19 to form 18-HETE or 19-HETE, respectively, though the physiological significance of this activity remains unclear. It also metabolizes ...
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Epoxydocosapentaenoic Acid
Epoxide docosapentaenoic acids (epoxydocosapentaenoic acids, EDPs, or EpDPEs) are metabolites of the 22-carbon straight-chain omega-3 fatty acid, docosahexaenoic acid (DHA). Cell types that express certain cytochrome P450 (CYP) epoxygenases metabolize polyunsaturated fatty acids (PUFAs) by converting one of their double bonds to an epoxide. In the best known of these metabolic pathways, cellular CYP epoxygenases metabolize the 20-carbon straight-chain omega-6 fatty acid, arachidonic acid, to epoxyeicosatrienoic acids (EETs); another CYP epoxygenase pathway metabolizes the 20-carbon omega-3 fatty acid, eicosapentaenoic acid (EPA), to epoxyeicosatetraenoic acids (EEQs). CYP epoxygenases similarly convert various other PUFAs to epoxides (see Epoxygenase). These epoxide metabolites have a variety of activities. However, essentially all of them are rapidly converted to their corresponding, but in general far less active, vicinal dihydroxy fatty acids by ubiquitous cellular soluble ...
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Epoxygenase
Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 (CYP450 or just CYP) enzymes that metabolize polyunsaturated fatty acids (PUFAs) to epoxide products that have a range of biological activities. The most thoroughly-studied substrate of the CYP epoxygenases is the PUFA arachidonic acid (AA). Eicosanoids are created from AA in three pathways: # Cyclooxygenases metabolize AA to various prostaglandin, thromboxane, and prostacyclin metabolites. # Lipoxygenases metabolize AA to hydroxyeicosatetraenoic acids (e.g. 5-HETE or 12-HETE) and leukotrienes (e.g. leukotriene B4 or leukotriene C4). # CYP epoxygenases metabolize AA to epoxyeicosatrienoic acids (EETs). Like the first two pathways, the third acts as a signaling pathway wherein the eicosatrienoic acid epoxide products work as secondary signals to activate their parent or nearby cells and thereby orchestrate functional responses. However, these enzymes are not limited to metabolizing AA to ...
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Epoxyeicosatetraenoic Acid
Epoxyeicosatetraenoic acids (EEQs or EpETEs) are a set of biologically active epoxides that various cell types make by metabolizing the omega 3 fatty acid, eicosapentaenoic acid (EPA), with certain cytochrome P450 epoxygenases. These epoxygenases can metabolize EPA to as many as 10 epoxides that differ in the site and/or stereoisomer of the epoxide formed; however, the formed EEQs, while differing in potency, often have similar bioactivities and are commonly considered together. Structure EPA is a straight-chain, 20 carbon omega-3 fatty acid containing ''cis'' double bonds between carbons 5 and 6, 8 and 9, 11 and 12, 14 and 15, and 17 and 18; each of these double bonds is designated with the notation ''Z'' to indicate its ''cis'' configuration in the IUPAC Chemical nomenclature used here. EPA is therefore 5''Z'',8''Z'',11''Z'',14''Z'',17''Z''-eicosapentaenoic acid. Certain cytochrome P450 epoxygenases metabolize EPA by converting one of these double bounds to an epoxide thereby ...
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Prostaglandin H2
Prostaglandin H2 (PGH2), or prostaglandin H2 (PGH2), is a type of prostaglandin and a precursor for many other biologically significant molecules. It is synthesized from arachidonic acid in a reaction catalyzed by a cyclooxygenase enzyme. The conversion from arachidonic acid to prostaglandin H2 is a two-step process. First, COX-1 catalyzes the addition of two free oxygens to form the 1,2-dioxane bridge and a peroxide functional group to form prostaglandin G2 (PGG2). Second, COX-2 reduces the peroxide functional group to a secondary alcohol, forming prostaglandin H2. Other peroxidases like hydroquinone have been observed to reduce PGG2 to PGH2. PGH2 is unstable at room temperature, with a half life of 90–100 seconds, so it is often converted into a different prostaglandin. It is acted upon by: * prostacyclin synthase to create prostacyclin * thromboxane-A synthase to create thromboxane A2 and 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) (see 12-Hydroxyheptadecatri ...
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Prostaglandin F2
Prostaglandin F2α (PGF2α in prostanoid nomenclature), pharmaceutically termed dinoprost, is a naturally occurring prostaglandin used in medicine to induce labor and as an abortifacient. Prostaglandins are lipids throughout the entire body that have a hormone-like function. In pregnancy, PGF2α is medically used to sustain contracture and provoke myometrial ischemia to accelerate labor and prevent significant blood loss in labor. Additionally, PGF2α has been linked to being naturally involved in the process of labor. It has been seen that there are higher levels of PGF2α in maternal fluid during labor when compared to at term. This signifies that there is likely a biological use and significance to the production and secretion of PGF2α in labor. Prostaglandin is also used to treat uterine infections in domestic animals. In domestic mammals, it is produced by the uterus when stimulated by oxytocin, in the event that there has been no implantation during the luteal phase. It a ...
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Prostaglandin E1
Prostaglandin E1 (PGE1) is a naturally occurring prostaglandin with various medical uses. Alprostadil and misoprostol are synthetic forms of prostaglandin E1 used as medications. Lubiprostone, a derivative of prostaglandin E1, is also used as a medication. Prostaglandin E1 is a vasodilator. It has various effects in the body that include opening blood vessels, relaxing smooth muscle, inhibiting clotting, and causing uterine contractions. In infants with certain congenital heart defects, alprostadil is delivered by slow injection into a vein to maintain a patent ductus arteriosus until surgery can be carried out. By injection into the penis or placement in the urethra, alprostadil is used to treat erectile dysfunction. Common side effects when given to babies include decreased breathing, fever, and low blood pressure. When injected into the penis for erectile dysfunction; side effects may include penile pain, bleeding at the site of injection, and prolonged erection (pr ...
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Prostaglandin E2
Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. In babies it is used in those with congenital heart defects until surgery can be carried out. It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein. PGE2 synthesis within the body begins with the activation of arachidonic acid (AA) by the enzyme phospholipase A2. Once activated, AA is oxygenated by cyclooxygenase (COX) enzymes to form prostaglandin endoperoxides. Specifically, prostaglandin G2 (PGG2) is modified by the peroxidase moiety of the COX enzyme to produce prostaglandin H2 (PGH2) which is then converted to PGE2. Common side effects of PGE2 include nausea, vomiting, diarrhea, fever, and excessi ...
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Prostaglandin D2
Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR (DP1), as well as CRTH2 (DP2). It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large amounts of PGD2 are found only in the brain and in mast cells. It is critical to development of allergic diseases such as asthma. Research carried out in 1989' found PGD2 is the primary mediator of vasodilation (the "niacin flush") after ingestion of niacin (nicotinic acid). A 2012 research paper indicates a causal link between elevated levels of localized PGD2 and hair growth inhibition. Applied topically, the researchers found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The researchers also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue, through increased levels of prostaglandin D2 synthase. The paper suggested th ...
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Leukotriene B4
Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. Biochemistry LTB4 is a leukotriene involved in inflammation. It is produced from leukocytes in response to inflammatory mediators and is able to induce the adhesion and activation of leukocytes on the endothelium, allowing them to bind to and cross it into the tissue. In neutrophils, it is also a potent chemoattractant, and is able to induce the formation of reactive oxygen species and the release of Lysosome, lysosomal enzymes by these cells. It is synthesized by leukotriene-A4 hydrolase from Leukotriene A4, leukotriene A4. Diabetes A study at the University of California, San Diego School of Medicine has shown that LTB4 promotes insulin resistance in obese mice. Obesity is the major cause of insulin resistance in type 2 diabetes. References

{{PPAR modulators Eicosanoids ...
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