Glucuronidation

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Glucuronidation is a well-known phase II detoxification reaction that acts as a pathway for eliminating many drugs, endogenous substances substances produced by the body such as hormones, neurotransmitters , estrogens , mold toxins , and cancer-causing toxins. During the glucuronidation process, the glucuronic acid part of the UDP-glucuronic acid is transferred to the toxins to make them:. The process of glucuronidation occurs in the liver , and the compound UDP-glucuronic acid or Uridine Diphosphate glucuronic acid is an intermediary product formed in the liver. The primary role of any detoxification pathway is to neutralize any compound or molecule that can harm the body. When toxins are not efficiently eliminated, they build up in the body, causing tissue and organ damage and giving rise to diseases like cancer. Glucuronidation, is an essential detoxification pathway in the elimination of a large number of drugs , hormones, bile acids, hydroxysteroids, tobacco products, and other endogenous and xenobiotic compounds not produced by the body but found in it toxic compounds. UGT or glucuronidation enzymes can be found throughout the body.

Glucuronidation

Federal government websites often end in. The site is secure. Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances. Although it is usually the secondary metabolic pathway for a compound preceded by phase I hydroxylation, glucuronidation alone could serve as the dominant metabolic pathway compounds, including some with high aqueous solubility. Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases UGTs into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters. Therefore, elimination of parent compound via glucuronidation in a metabolic active cell is controlled by two driving forces; the formation of glucuronides by UGT enzymes and the polarized excretion of these glucuronides by efflux transporters located on the cell surfaces in various drug disposition organs. Contrary to the common assumption that the glucuronides reaching the systemic circulation were destined for urinary excretion, recent evidences suggest that hepatocytes are capable of highly efficient biliary clearance of the gut-generated glucuronides. Furthermore, the biliary- and enteric-eliminated glucuronides participate into recycling schemes involving intestinal microbes, which often prolong their local and systemic exposure, albeit at low systemic concentrations. Taken together, these recent research advances indicate that though UGT determines the rate and extent of glucuronide generation, the efflux and uptake transporters determine the distribution of these glucuronides into blood and then to various organs for elimination. Recycling schemes impact the apparent plasma half-life of parent compounds and their glucuronides that reach intestinal lumen, in addition to prolonging their gut and colon exposure.

Drug Metab Dispos 31 —

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. 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. 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 glucuronidation to make a large variety of substances more water-soluble, and, in this way, allow for their subsequent elimination from the body through urine or feces via bile from the liver.

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Glucuronidation

Federal government websites often end in. The site is secure. Glucuronidation is a well-recognized phase II metabolic pathway for a variety of chemicals including drugs and endogenous substances.

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Steroids 7 — Although not frequently reported, hydrophilic molecules are sometimes also glucuronidated. Cruciferous vegetables such as broccoli, Brussel sprouts, cauliflower, etc. UGT Enzyme-efflux transporter interplay has been investigated extensively in last decade, however, other coupling mechanisms with respect to xenobiotic glucuronidation are yet to be explored in depth. Drug Metab Rev. It was worth it. Ezetimibe Ezzet et al. FEBS Lett — OATPs provides a potential pathway for extrahepatically generated glucuronides to be excreted into bile and therefore enhances the enterohepatic circulation of glucuronide conjugates. Mrp5 is also the main anionic conjugate efflux transporter at the basolateral side and is ubiquitous in many organs Klaassen and Aleksunes, ; Chen and Tiwari, ; Kock and Brouwer, Perfect and very usefull!

The liver is the principal site of drug metabolism for review, see [ 1 General references The liver is the principal site of drug metabolism for review, see [ 1]. Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even

Enterohepatic Recycling. Xenobiotica 11 — A list of compounds with their secondary metabolic pathway as glucuronidation. This prospect is equally important in the case of locally active drugs such as ezetimibe and ezetimibe glucuronide more active than the parent compound , which exerts their cholesterol-lowering action by reducing the uptake and absorption of cholesterol by enterocytes. There are various reports of a linkage between disease severity and expression level in both humans and rats. Yao Xue Xue Bao 47 — Respir Res 6 For example, morphineglucuronide is reported to be 45—61 folds more potent Frances et al. For Mrp7, Mrp8, and Mrp9, their specific locations of expression are less clear and appear to be random Cai and Gros, ; Marquez et al. The presence of these transporters provides a pathway for hepatic excretion and facilitates enterohepatic recycling. More recently, the Mrp family of efflux transporters has become known to efflux sulfate, glucuronide, and glutathione metabolites into the interstitial space, bile duct, intestinal lumen and basolateral surface of hepatocytes and enterocytes Keppler and Konig, ; Jemnitz et al. Cruciferous vegetables such as broccoli, Brussel sprouts, cauliflower, etc. Curr Drug Metab 4 —