Редактирование: UGT1A10 (раздел)

==Publications==

{{medline-entry
|title=Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase [[UGT1A4]], [[UGT1A8]], and [[UGT1A1]]0.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18838507
|abstract=Valproic acid (VPA) is a widely used anticonvulsant that is also approved for mood disorders, bipolar depression, and migraine. In vivo, valproate is metabolized oxidatively by cytochromes P450 and beta-oxidation, as well as conjugatively via glucuronidation. The acyl glucuronide conjugate (valproate-glucuronide or VPAG) is the major urinary metabolite (30-50% of the dose). It has been hypothesized that glucuronidation of antiepileptic drugs is spared over age, despite a known decrease in liver mass. The formation rates of VPAG in a bank of elderly (65 years onward) human liver microsomes (HLMs) were measured by liquid chromatography/tandem mass spectrometry and compared with those in a younger (2-56 years) HLM bank. In vitro kinetic studies with recombinant UDP-glucuronosyltransferases (UGTs) were completed. A 5- to 8-fold variation for the formation of VPAG was observed within the microsomal bank obtained from elderly and younger donors. VPAG formation ranged from 6.0 to 53.4 nmol/min/mg protein at 1 mM substrate concentration (n=36). The average velocities at 0.25, 0.5, and 1 mM VPA were 7.0, 13.4, and 25.4 nmol/min/mg protein, respectively, in the elderly HLM bank. Rates of VPAG formation were not significantly different in the HLM bank obtained from younger subjects. Intrinsic clearances (V(max)/K(m)) for several cloned, expressed UGTs were determined. [[UGT1A4]], [[UGT1A8]], and [[UGT1A1]]0 also were found to catalyze the formation of VPAG in vitro. This is the first reported activity of these UGTs toward VPA glucuronidation. [[UGT2B7]] had the highest intrinsic clearance, whereas [[UGT1A1]] demonstrated no activity. In conclusion, our investigation revealed no differences in VPAG formation in younger versus elderly HMLs and revealed three other UGTs that form VPAG in vitro.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Child
* Child, Preschool
* Chromatography, High Pressure Liquid
* Glucuronides
* Glucuronosyltransferase
* Humans
* Isoenzymes
* Microsomes, Liver
* Middle Aged
* Reference Standards
* Tandem Mass Spectrometry
* Valproic Acid

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683660
}}