UDP-glucuronosyltransferases (UGTs) play a major role in the conjugation and therefore elimination of potentially toxic xenobiotics and endogenous compounds. The 1-4 isoform UGT1A4 is able to act upon lipophilic bilirubin, the end product of heme breakdown. Defects in UGT1A4 can cause hyperbilirubinemia syndromes ranging from mild forms such as Gilbert syndrome (GILBS; MIM:143500) to the more severe Crigler-Najjar syndromes 1 and 2 (CN1, CN2; MIM:218800 and MIM:606785) (Sticova & Jirsa 2013, Strassburg 2010, Udomuksorn et al. 2007, Costa 2006, Maruo et al. 2000).
The principal conjugate of bilirubin in bile is bilirubin diglucuronide (BDG). UGT1A4 can transfer glucuronic acid (GlcA) to bilirubin (BIL) and bilirubin monoglucuronide (BMG) to form both the monoglucuronide and the diglucuronide (BDG) conjugates respectively (Ritter et al. 1992).
Bilirubin (BIL) is a breakdown product of heme. Its accumulation in the blood can be fatal. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. Both UGT1A1 tetramer and UGT1A4 can transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugates (Bosma et al. 1994, Ritter et al. 1992, Peters & Jansen 1986, Gorden et al. 1983, Choudhury et al. 1981, Fevery et al. 1971).
Bilirubin (BIL) is a breakdown product of heme, causing death if allowed to accumulate in the blood. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. UGT1A1 and 4 are the only enzymes that transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugate. Defects in UGT1A4 can cause hyperbilirubinemia syndromes ranging from mild forms such as Gilbert syndrome (GILBS; MIM:143500) to the more severe Crigler-Najjar syndromes 1 and 2 (CN1, CN2; MIM:218800 and MIM:606785). A mutation causing the severest form, CN1, is S376F (Bosma et al. 1992).
Bilirubin (BIL) is a breakdown product of heme, causing death if allowed to accumulate in the blood. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. UGT1A1 and 4 are the only enzymes that transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugate. Defects in UGT1A4 can cause hyperbilirubinemia syndromes ranging from mild forms such as Gilbert syndrome (GILBS; MIM:143500) to the more severe Crigler-Najjar syndromes 1 and 2 (CN1, CN2; MIM:218800 and MIM:606785). A mutation causing the severest form, CN1, is S376F (Bosma et al. 1992).
Bilirubin (BIL) is a breakdown product of heme. Its accumulation in the blood can be fatal. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. Both UGT1A1 tetramer and UGT1A4 can transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugates (Bosma et al. 1994, Ritter et al. 1992, Peters & Jansen 1986, Gorden et al. 1983, Choudhury et al. 1981, Fevery et al. 1971).