Multiplicity of mutation in UDP-glucuronosyltransferase 11 gene in Gilbert's syndrome

Kamisako, Toshinori; Soeda, Yoko; Yamamoto, Kazuo; Sato, Hiroshi; Adachi, Yukihiko

doi:10.1016/s0928-4346(97)00354-x

Cited by 6 publications

(1 citation statement)

References 9 publications

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“…[24][25][26] Mutations described in patients with Crigler-Najjar syndrome type II are nonsense mutations (heterozygous), missense mutations in exons 1A, 2, and 5 (homozygous and compound heterozygous), and frame shifts. [26][27][28][29] Two types of UGT1A1 mutations, a homozygous TA insertion in the TATA box of the promoter region, and a missense mutation (heterozygous in most patients) in the coding region, [30][31][32] were reported in patients with Gilbert's syndrome.…”

Section: Mechanism Of Bilirubin Transport Across the Hepatocyte Sinusmentioning

confidence: 99%

Recent advances in bilirubin metabolism research: the molecular mechanism of hepatocyte bilirubin transport and its clinical relevance

Kamisako

Kobayashi

Takeuchi

et al. 2000

Journal of Gastroenterology

137

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Bilirubin is taken up from blood into hepatocytes by sinosuidal membrane transporters and then excreted into bile through the bile canalicular membrane mainly as bilirubin glucuronides. (1) Mechanism of bilirubin uptake into hepatocytes: many organic anions are incorporated into hepatocytes by organic anion transporting polypeptides (rat, oatp1, oatp2, oatp3; human, OATP), liver-specific transporter (rlst/HLST), and/or by organic anion transporters (OAT2, OAT3). Oatp1 and HLST transport bilirubin monoglucuronide. However, a transporter of unconjugated bilirubin in the sinusoidal membrane has not as yet been identified. Unconjugated bilirubin may also go across the hepatocyte sinusoidal membrane by a diffusion process. (2) Intrahepatic transport and conjugation of bilirubin: ligandin carries bilirubin to the endoplasmic reticulum (ER) of hepatocytes. In the ER, bilirubin is conjugated by bilirubin uridine diphosphate (UDP)-glycosyltransferase (bilirubin UGT; UGT1A1) to form mono- and diglucuronides of bilirubin. (3) Transport mechanism of bilirubin glucuronides across the hepatocyte canalicular membrane: at the canalicular membrane, bilirubin glucuronides are excreted into bile by multidrug resistance-associated protein 2 (MRP2), a member of the ATP-binding cassette transporter family. (4) Regurgitation of bilirubin glucuronides into blood: MRP3, which is located in the lateral membrane, transports bilirubin glucuronides into blood under conditions of impaired biliary bilirubin excretion.

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