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home - Liver - Bilirubin Metabolism - Bilirubin Metabolism 2 Written by Dr Sebastian Zeki

Bilirubin Metabolism 2

endoplasmic reticulum (ER) Glucuronidation of bilirubin, a large variety of endogenous compounds (eg, steroid hormones, thyroid hormones, catecholamines), and a wide array of exogenous substrates (eg, drugs, toxins, carcinogens and laboratory xenobiotics) is mediated by a family of enzymes, termed uridine-diphosphoglucuronate glucu-ronosyltransferase (UGT) UGT1A1 subtype of UGT is physiologically important in bilirubin glucuronidation. UGT1A1 is an intrinsic protein of the endoplasmic reticulum (ER) and its catalytic site is located within the ER lumen. Bilirubin diglucuronide makes up 80 % of bile.If reduced bilirubin-UGT activity, the propor-tion of bilirubin monoglucuronide can Inhibitory factor(s) for hepatic UGT1A1 is secreted in the milk of some mothers (maternal milk jaundice). Inhibitory factor in maternal plasma can cross placenta (Lucey Driscoll sndrome). UGT1A1 deficiency also may be seen in neonates, chronic hepatitis, and in inherited disorders (Gilbert's syndrome and Crigler-Najjar syndrome I and II). Conjugation: Glucuronic acid conjuga-tion of the propionic acid side chains of bilirubin renders it water soluble and therefore non-toxic and easy to eliminate.Bilirubin is excreted into bile as the diglucuron-ides. Water soluble Bilirubin glucuronides Impaired hepatic bilbirubin uptakeCCFPortosystemic shuntsSome patients with Gilbert’s syndromeCertain drugs- rifampicin, probenicid Impaired bilirubin conjugationCrigler-Najjar syndrome type I and IIGilbert’s syndromeNeonatesHyperthyroidismEthinyl estradiolLiver diseases Bilirubin-glutathione S-transferases (GSTs) bound Conjugation of bilirubin Glucose UDP-Glucose UDP-Glucoronate Bilirubin glucoronide Bilirubin monoglucoronide Bilirubin diglucoronide UDP gluc-oronic acid Bilirubin Transferase UDP glucose dehydroge- UDP glucose pyrophosphatase The sugar donor substrate uridinediphos-phoglucuronate (UDPGA) must enter the ER lume-nal space for conjugation.UDP-N-acetylglucosamine is the natural stimulator of the transport of the polar substrate, UDPGA into the ER lumen. Written by Dr Sebastian Zeki

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