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UDP-glucuronosyltransferase
Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UGT) is a microsomal glycosyltransferase () that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction. ''Alternative names:'' *glucuronyltransferase *UDP-glucuronyl transferase *UDP-GT Function Glucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxin ...
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UGT1A3
UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the ''UGT1A3'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo(a)pyrene Benzo 'a''yrene (B''a''P or B ) is a polycyclic aromatic hydrocarbon and the result of in ...
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UGT1A4
UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the ''UGT1A4'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5′ exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although it is more active on amines, steroids, and sapogenin Sapogenins are the aglycones, or non-saccharide, portions ...
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UGT1A1
UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the ''UGT1A1'' gene. UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT), an enzyme of the glucuronidation pathway that transforms small lipophilic (fat-soluble) molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. Gene The UGT1A1 gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternative first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Over 100 genetic variants within the UGT1A1 gene have been described, some of which confer ...
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Glucuronidation
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds. Mechanism Glucuronidation consists of transfer of the glucuronic acid component of uridine diphosphate glucuronic acid to a substrate by any of several types of UDP-glucuronosyltransferase. UDP-glucuronic acid (glucuronic acid linked via a glycosidic bond to uridine diphosphate) is an intermediate in the process and is formed in the liver. One example is the N-glucuronidation of an aromatic amine, 4-aminobiphenyl, by UGT1A4 or UGT1A9 from human, rat, or mouse liver. : The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water-soluble than the non-glucuronic acid-containing substances from which they were originally synthesised. The human body uses gl ...
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Gilbert's Syndrome
Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice (a slight yellowish color of the skin or whites of the eyes) may occur. Gilbert syndrome is due to a genetic variant in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of variant. Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating. Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown. Typically no treatment is needed. Gilbert syndrome is associated with decreased cardiovascular health risks. If jaundice is significant phenobarbital may be used, which aids ...
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Phase II Metabolism
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds (although in some cases the intermediates in xenobiotic metabolism can themselves cause toxic effects). The study of drug metabolism is called pharmacokinetics. The metabolism of pharmaceutical drugs is an important aspect of pharmacology and medicine. For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Drug metabolism also affec ...
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Glucuronic Acid
Glucuronic acid (from Greek γλεῦκος "''wine, must''" and οὖρον "''urine''") is a uronic acid that was first isolated from urine (hence the name). It is found in many gums such as gum arabic (c. 18%), xanthan, and kombucha tea and is important for the metabolism of microorganisms, plants and animals. Properties Glucuronic acid is a sugar acid derived from glucose, with its sixth carbon atom oxidized to a carboxylic acid. In living beings, this primary oxidation occurs with UDP-α-D-glucose (UDPG), not with the free sugar. Glucuronic acid, like its precursor glucose, can exist as a linear (carboxo-)aldohexose ( 60,000 are too large for renal excretion and will be excreted with bile into the intestine. Neonates are deficient in this conjugating system, making them particularly vulnerable to drugs such as chloramphenicol, which is inactivated by the addition of glucuronic acid, resulting in gray baby syndrome. Bilirubin is excreted in the bile as bilirubin ...
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Heart Failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling. The shortness of breath may occur with exertion or while lying down, and may wake people up during the night. Chest pain, including angina, is not usually caused by heart failure, but may occur if the heart failure was caused by a heart attack. The severity of the heart failure is measured by the severity of symptoms during exercise. Other conditions that may have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease. Common causes of heart failure include coronary artery disease, heart attack, high blood pressure, atrial fibrillation, valvular heart disease, excessive alcohol consumption, infection, and cardiomyopathy. These cause heart failure by alterin ...
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Medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management. Drugs are classified in multiple ways. One of the key divisions is by level of control, which distinguishes prescription drugs (those that a pharmacist dispenses only on the order of a physician, physician assistant, or qualified nurse) from over-the-counter drugs (those that consumers can order for themselves). Another key distinction is between traditional small molecule drugs, usually derived from chemical synthesis, and biopharmaceuticals, which include recombinant proteins, vaccines, blood products used therapeutically (such as IVIG), gene therapy, monoclonal antibodies and cell therapy (for instance, stem cell th ...
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Ethinyl Estradiol
Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring. The general side effects of EE include breast tenderness and enlargement, headache, fluid retention, and nausea among others. In men, EE can additionally cause breast development, feminization in general, hypogonadism, and sexual dysfunction. Rare but serious side effects include blood clots, liver damage, and cancer of the uterus. EE is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol. It is a synthetic derivative of estradiol, a natural estrogen, and differs from it in various ways. Compared to estradiol, EE has greatly improved bioavailability when tak ...
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Chronic Hepatitis
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is ''acute'' if it resolves within six months, and '' chronic'' if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer. Hepatitis is most commonly caused by the virus ''hepatovirus A'', '' B'', '' C'', '' D'', and '' E''. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever virus. Other common causes of hepatitis include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (NASH). Hepatiti ...
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B3GAT2
Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 is an enzyme that in humans is encoded by the ''B3GAT2'' gene. The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes the transfer of a beta-1,3 linked glucuronic acid to a terminal galactose in different glycoproteins or glycolipids containing a Gal-beta-1-4GlcNAc or Gal-beta-1-3GlcNAc residue. The encoded protein is involved in the synthesis of the human natural killer-1 (HNK-1) carbohydrate epitope, a sulfated trisaccharide implicated in cellular migration and adhesion in the nervous system. Use of HNK-1 Antibody for Neural Crest Research Antibodies raised against the HNK-1 epitope have played a large role in studies of the neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage ...
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