Defective UGT1A4 does not transfer GlcA from UDP-GlcA to BMG

Stable Identifier
R-HSA-9036104
Type
Reaction [transition]
Species
Homo sapiens
Compartment
endoplasmic reticulum membrane, endoplasmic reticulum lumen
ReviewStatus
5/5
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Defective UGT1A4 does not transfer GlcA from UDP-GlcA to BMG
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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).
Literature References
PubMed ID Title Journal Year
1634050 Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I

Bosma, PJ, Chowdhury, JR, Huang, TJ, Lahiri, P, Elferink, RP, Van Es, HH, Lederstein, M, Whitington, PF, Jansen, PL, Chowdhury, NR

FASEB J. 1992
Participants
Input
Participates
as an event of
Catalyst Activity

glucuronosyltransferase activity of UGT1A4 S376F [endoplasmic reticulum membrane]

Physical Entity
UGT1A4 S376F [endoplasmic reticulum membrane] (Homo sapiens)
Activity
glucuronosyltransferase activity (GO:0015020)
Normal reaction
UGT1A4 transfers GlcA from UDP-GlcA to BMG to form BDG (Homo sapiens)
Functional status

Loss of function of UGT1A4 S376F [endoplasmic reticulum membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
Crigler-Najjar syndrome DOID:3803 Bilirubin UDP glucuronyl transferase deficiency, Crigler Najjar syndrome, Crigler-Najjar syndrome (disorder), Crigler-Najjar syndrome, Crigler-Najjar syndrome, type I (disorder)
Cross References
Mondo
Authored
Jassal, B  (2014-07-03)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-07-03)
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