Редактирование: UGT1A8 (раздел)

==Publications==

{{medline-entry
|title=Microsomal quercetin glucuronidation in rat small intestine depends on age and segment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21543555
|abstract=UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in three equidistant small intestine ([[SI]]) segments from 4-, 12-, 18-, and 28-month-old male Fischer 344 rats (n = 8/age) using villin to control for enterocyte content. [[SI]] microsomal intrinsic clearance of quercetin was increased 3- to 9-fold from 4 months in the proximal and distal [[SI]] at 12 and 18 months. Likewise, at 30 μM quercetin, [[SI]] microsomal glucuronidation activity was increased with age: 4.8- and 3.9-fold greater at 18 months than at 4 months. Quercetin UGT regioselectivity was not changed by age. The distal [[SI]] preferentially catalyzed glucuronidation at the 7-position, whereas the proximal [[SI]] produced the greatest proportion of 4'- and 3'-conjugates. Enterocyte UGT content in different [[SI]] segments was not consistently changed with age. In the proximal [[SI]], UGT1A increased 64 and 150% at 12 and 18 months and [[UGT1A1]], [[UGT1A7]], and [[UGT1A8]] were also increased at 12 and 18 months. However, age-related changes in expression were inconsistent in the medial and distal segments. Microsomal rates of quercetin glucuronidation and UGT expression were positively correlated with [[UGT1A1]] content for all pooled samples (r = 0.467) and at each age (r = 0.538-0.598). [[UGT1A7]] was positively correlated with total, 7-O- and 3-O-quercetin glucuronidation at 18 months. Thus, age-related differences in UGT quercetin glucuronidation depend on intestinal segment, are more pronounced in the proximal and distal segments and may be partially related to [[UGT1A1]] and [[UGT1A7]] content.
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Chromatography, High Pressure Liquid
* Dose-Response Relationship, Drug
* Enterocytes
* Glucuronides
* Glucuronosyltransferase
* Intestinal Mucosa
* Intestine, Small
* Male
* Microsomes
* Quercetin
* Rats
* Rats, Inbred F344

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141883
}}
{{medline-entry
|title=[[UGT1A9]] -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19494809
|abstract=Mycophenolate mofetil (MMF) is an immunosuppressive drug commonly used in the context of kidney transplantation. Exposure to the active metabolite mycophenolic acid (MPA) is associated with risk of allograft rejection. MPA pharmacokinetics varies between individuals, the potential cause being the presence of genetic polymorphisms in key enzymes. We genotyped 338 kidney transplant patients for [[UGT1A8]], [[UGT1A9]], [[UGT2B7]], and MRP2 polymorphisms and recorded MPA exposure and biopsy-proven acute rejections (BPARs) during a 1-year follow-up. Tacrolimus-treated patients who were [[UGT1A9]] -275T>A and/or -2152C>T carriers displayed a 20% lower MPA area under the concentration-time curve from 0 to 12 h (AUC(0-12)) (P = 0.012). [[UGT1A9]]*3 carriers displayed a 49% higher MPA AUC(0-12) when treated with tacrolimus and a 54% higher MPA AUC(0-12) when treated with cyclosporine (P < 0.005). Cyclosporine-treated [[UGT1A8]]*2/*2 (518GG) patients had an 18% higher MPA AUC(0-12) compared with noncarriers. Carrying the [[UGT1A9]] -275T>A and/or -2152C>T polymorphism significantly predicted acute rejection in fixed-dose (FD) MMF-treated patients receiving tacrolimus (odds ratio 13.3, 95% confidence interval 1.1-162.3; P < 0.05). [[UGT1A9]] -275T>A and/or -2152C>T genotyping may identify patients at risk of MPA underexposure and acute rejection when receiving treatment with MMF and tacrolimus.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aging
* Antibiotics, Antineoplastic
* Area Under Curve
* Calcineurin Inhibitors
* Creatinine
* Female
* Glucuronosyltransferase
* Graft Rejection
* Humans
* Immunosuppressive Agents
* Kidney Transplantation
* Male
* Middle Aged
* Multidrug Resistance-Associated Proteins
* Mycophenolic Acid
* Polymorphism, Genetic
* Prospective Studies
* Sex Characteristics
* Tacrolimus
* Treatment Outcome
* Young Adult

|full-text-url=https://sci-hub.do/10.1038/clpt.2009.83
}}
{{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
}}