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CYP2J2
Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the ''CYP2J2'' gene. CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids. Protein structure The CYP2J2 contains the following domains: • Hydrophobic binding domains • F-G loop (containing non-conservative mutations) primary membrane binding motif The protein also contains an N-terminal anchor. F-G loop The F-G loop mediates the binding and passage of substrates, and its hydrophobic region containing residues Trp-235, Phe-239 and Ille-236 allows the enzyme to interact with cellular membranes. Mutations to hydrophilic residues in the F-G loop alter the binding mechanism by changing insertion depth of the enzyme into the membrane. Tissue distribution CYP2J2 is expressed predominately in the heart and ...
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Epoxyeicosatrienoic Acid
The epoxyeicosatrienoic acids or EETs are signaling molecules formed within various types of cells by the metabolism of arachidonic acid by a specific subset of Cytochrome P450 enzymes termed cytochrome P450 epoxygenases. These nonclassic eicosanoids are generally short-lived, being rapidly converted from epoxides to less active or inactive dihydroxy-eicosatrienoic acids (diHETrEs) by a widely distributed cellular enzyme, Soluble epoxide hydrolase (sEH), also termed Epoxide hydrolase 2. The EETs consequently function as transiently acting, short-range hormones; that is, they work locally to regulate the function of the cells that produce them (i.e. they are autocrine agents) or of nearby cells (i.e. they are paracrine agents). The EETs have been most studied in animal models where they show the ability to lower blood pressure possibly by a) stimulating arterial vasorelaxation and b) inhibiting the kidney's retention of salts and water to decrease intravascular blood volume. In ...
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Epoxygenase
Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 (CYP P450 or just CYP) enzymes that metabolize polyunsaturated fatty acids to epoxide products that have a range of biological activities. The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. This polyunsaturated fatty acid is metabolized by cyclooxygenases to various prostaglandin, thromboxane, and prostacyclin metabolites in what has been termed the first pathway of eicosanoid production; it is also metabolized by various lipoxygenases to hydroxyeicosatetraenoic acids (e.g. 5-Hydroxyeicosatetraenoic acid, 12-Hydroxyeicosatetraenoic acid, 15-hydroxyicosatetraenoic acid) and leukotrienes (e.g. leukotriene B4, leukotriene C4) in what has been termed the second pathway of eicosanoid production. The metabolism of arachidonic acid to epoxyeicosatrienoic acids by the CYP epoxygenases has been termed the third pathway of eicosanoid metabolism. Like the first two pathways of eic ...
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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 acid's (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 (chemistry) dihydroxy fatty acids by ubiquitous cellu ...
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CYP2C9
Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the ''CYP2C9'' gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme. Function CYP2C9 is a crucial cytochrome P450 enzyme, which plays a significant role in the metabolism, by oxidation, of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes. The protein is mainly expressed in liver, duodenum and small intestine. About 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 extr ...
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CYP2C8
Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and Linoleic acid to their biologically active epoxides. Ligands Following is a table of selected substrates, inducers and inhibitors of 2C8. Inhibitors of CYP2C8 can be classified by their potency, such as: *Strong inhibitor being one that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance. *Moderate inhibitor being one that causes at least a two-fold increase in the plasma AUC values, or 50-80% decrease in clearance. *Weak inhibitor being one that causes at least a 1.25-fold but less than two-fold increase in the plasma AUC values, or 20-50% decrease in clearance. Retrieved on July ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Stomach Carcinoma
Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymphomas and mesenchymal tumors may also develop in the stomach. Early symptoms may include heartburn, upper abdominal pain, nausea, and loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing, and blood in the stool, among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen, and lymph nodes. The most common cause is infection by the bacterium ''Helicobacter pylori'', which accounts for more than 60% of cases. Certain types of ''H. pylori'' have greater risks than others. Smoking, dietary factors such as pickled vegetables and obesity are other risk factors. About 10% of ...
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Breast Carcinoma
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with Metastatic breast cancer, distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or jaundice, yellow skin. Risk factors for developing breast cancer include obesity, a Lethargy, lack of physical exercise, alcoholism, hormone replacement therapy during menopause, ionizing radiation, an early age at menarche, first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer, and a family history of breast cancer. About 5–10% of cases are the result of a genetic predisposition inherited from a person's parents, including BRCA1 and BRCA2 among others. Breast cancer most commonly ...
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Adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them. In the most specific usage (narrowest sense), the glandular origin or traits are exocrine; endocrine gland tumors, suc ...
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Inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair. The five cardinal signs are heat, pain, redness, swelling, and Functio laesa, loss of function (Latin ''calor'', ''dolor'', ''rubor'', ''tumor'', and ''functio laesa''). Inflammation is a generic response, and therefore it is considered as a mechanism of innate immune system, innate immunity, as compared to adaptive immune system, adaptive immunity, which is specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. b ...
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Myocardial Infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck or jaw. Often it occurs in the center or left side of the chest and lasts for more than a few minutes. The discomfort may occasionally feel like heartburn. Other symptoms may include shortness of breath, nausea, feeling faint, a cold sweat or feeling tired. About 30% of people have atypical symptoms. Women more often present without chest pain and instead have neck pain, arm pain or feel tired. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure, an irregular heartbeat, cardiogenic shock or cardiac arrest. Most MIs occur due to coronary artery disease. Risk factors include high blood pressure, smoking, diabetes, ...
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Hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high blood pressure, however, is a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide. High blood pressure is classified as primary (essential) hypertension or secondary hypertension. About 90–95% of cases are primary, defined as high blood pressure due to nonspecific lifestyle and genetic factors. Lifestyle factors that increase the risk include excess salt in the diet, excess body weight, smoking, and alcohol use. The remaining 5–10% of cases are categorized as secondary high blood pressure, defined as high blood pressure due to an identifiable cause, such ...
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