UDP-glucuronosyltransferase 1A4

Definition:

[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis. Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption.; [Isoform 2]: Lacks UDP-glucuronosyltransferase (UGT) activity but acts as a negative regulator of isoform 1.

References:

[1]. Hugo Girard, et al. Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity. Pharmacogenet Genomics. 2007 Dec;17(12):1077-89. [Content Brief]

[2]. Takanori Hashizume, et al. Identification of human UDP-glucuronosyltransferases catalyzing hepatic 1alpha,25-dihydroxyvitamin D3 conjugation. Biochem Pharmacol. 2008 Mar 1;75(5):1240-50. [Content Brief]

[3]. Zhican Wang, et al. Human UGT1A4 and UGT1A3 conjugate 25-hydroxyvitamin D3: metabolite structure, kinetics, inducibility, and interindividual variability. Endocrinology. 2014 Jun;155(6):2052-63. [Content Brief]

[4]. Judith Bellemare, et al. Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro. Drug Metab Dispos. 2010 Oct;38(10):1785-9. [Content Brief]

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