Uridine diphosphate glucuronic acid conjugation

F5. Fevery, J., Leroy, P., Van De Vijver, M., and Heirwegh, K. P. M., Structures of bilirubin conjugates synthesized in vitro from bilirubin and uridine diphosphate glucuronic acid, uridine diphosphate glucose or uridine diphosphate xylose by preparations from rat liver. Biochem. J. 129, 635-644 (1972). 

Typical reactions catalyzed by UGT enzymes require the cofactor uridine diphosphate-glucuronic acid, UDPGA. However, the C-terminus of all UGT enzymes contains a membrane-spanning domain that anchors the enzyme in the endoplasmic reticulum, and the enzyme faces the lumen of the endoplasmic reticulum, where it is ideally placed to conjugate lipophilic xenobiotics and their metabolites generated by oxidation, reduction, or hydrolysis. The lumenal... 

Fig. 4 Formation of uridine diphosphate glucuronic acid (UDP-GA) and its conjugation with clofibric acid. Inversion takes place during conjugation, the a-D-glucuronic acid forming a P-D-glucuronide. At a more alkaline pH, such glu-curonides may undergo intramolecular rearrangement to forms resistant to enzymic hydrolysis by P-glucuronidase.

Conjugation reactions in which electrophilic adenosine-containing cofactors such as ATP, phosphoadenosine phosphosulfate (PAPS), acet-ylcoenzyme A (acetylCoA), uridine diphosphate glucuronic acid (UDPGA), or S-adenosylmethio-nine (SAM) react with nucleophilic groups such as -OH or -NHg... 

Catalyzes conjugation of uridine diphosphate glucuronic acid (UDPGA) to lipophilic substrates... 

Glucuronic acid conjugates were formed when phenols, epoxides, or dihydrodiols of BaP were incubated with uridine diphosphate glucuronic acid (UDPG) in the presence of rat liver microsomes. The conjugates were not formed when the soluble fraction was employed. Conjugates were formed most readily from the phenolic metabolites of BaP 358). 

The mechanism of steroid conjugation at the molecular level was demonstrated in the liver, and the role of active sulfate (3 -phosphoadenosine 5 -phosphosulfate) and of uridine diphosphate glucuronic acid was shown (see reviews in Roy, 196( Dutton, 1966). 

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