Glucuronosyltransferase (UGT)

Glucuronosyltransferase (UGT) is a glycosyltransferase (EC 2.4.1.17) also known as UDP-glucuronosyltransferase, that catalyzes the addition of a glycosyl group from a UTP-sugar to a small hydrophobic molecule.

Although the majority of UGT enzymes are expressed in the liver, UGT1A7, UGT1A8, and UGT1A10 are expressed exclusively extrahepatically, mainly in the intestine. UGT1A9, UGT2B7, and UGT2B11 are expressed at relatively high amounts in the kidney.[6]

Glucuronosyltransferase catalyzes the conversion of 1-naphthol + UDPglucuronate to 1-naphthyl-O-glucuronide + UDP.

Substrate UGT End Product
1-Naphthol 1-naphthyl-O-glucuronide
1-naphthol.png 1-Naphthyl_glucuronide.png
Cofactor Byproduct
UDPglucuronate UDP
UDPglucuronate.png UDP.png

UGT1A1

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] IC50 5.00 micorg/mL ?
Genistein (in Kudzu) 96.7% Inhibition [12] 30 μM ?
Isoliquiritigenin (in licorice) 95.2% [8] 100 μM ?
Liquiritigenin (in licorice) K(i) 9.1 μM [9] ? ?
Silybin IC50 1.4 µM [6] ? ?
Silymarin [6] ? ? ?
Valerenic acid [6] ? ? ?
Valerian root [6] ? ? ?

UGT1A3

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] 1.70 microg/mL ?
Genistein (in Kudzu) 47.4% Inhibition [12] 30 μM ?
Glycyrrhetinic acid (in licorice) K(i) 0.2  μM [10] ? ?
Isoliquiritigenin (in licorice) 76.1% [8] 100 μM ?

UGT1A4

Inhibitors Strength Dosage Verified in Man
EGCG IC50 33.8 μg/ml [3] ? ?

UGT1A6

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] IC50 5.66 microg/mL ?
Celastrol 99% inhibition[7] 100 μM ?
Isoliquiritigenin (in licorice) 78.9% [8] 100 μM ?
Milk thistle (contains silybin & silymarin) IC50 59.5 μg/ml [3] ? ?
Saw palmetto IC50 >100 μg/ml [3] ? ?
Silybin IC50 28 µM [6] ? ?
Silymarin [6] ? ? ?
Valerian root 75% inhibition [2]1 ? ?

UGT1A7

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] IC50 9.88 microg/mL ?
Isoliquiritigenin (in licorice) 87.2% [8] 100 μM ?

UGT1A8

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] IC50 2.57 microg/mL ?
Isoliquiritigenin (in licorice) 67.2% [8] 100 μM ?

UGT1A9

Inhibitors Strength Dosage Verified in Man
Genistein (in Kudzu) 79.5% Inhibition [12] 30 μM ?
Isoliquiritigenin (in licorice) 94.8% [8] 100 μM ?
Liquiritigenin (in licorice) K(i) 3.2 μM [9] ? ?
Milk thistle (contains silybin & silymarin) IC50 33.6 μg/ml [3] ? ?
Cranberry IC50 >100 μg/ml [3] ? ?
Silybin IC50 20 µM [6] ? ?
Silymarin [6] ? ? ?
Valerian root 75% inhibition [2]2 ? ?
Inducers Strength Dosage Verified in Man
Carbamazepine ? ? ?
Nicotine ? ? ?

UGT1A10

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] IC50 15.66 microg/mL ?
Isoliquiritigenin (in licorice) 91.7% [8] 100 μM ?

UGT2B4

Inhibitors Strength Dosage Verified in Man
Methadone ? ? Yes[4]

UGT2B7

Inhibitors Strength Dosage Verified in Man
Andrographis paniculata 50% [11] IC50 2.82 microg/mL ?
Atovaquone ? ? ?
(±) Borneol (rosemary essential oil) IC50=200 μM3[13] ? ?
(-) Borneol IC50=200 μM4[13] ? ?
Celastrol 98% inhibition[7] 100 μM ?
Dextropropoxyphene ? ? Yes[5]
Eugenol 54.5% inhibition [1] 100 μM ?
Fluconazole ? ? Yes[5]
Genistein (in Kudzu) 30% Inhibition [12] 30 μM ?
Glycyrrhetinic acid (in licorice) K(i) 1.7 μM [10] ? ?
(±) Isoborneol (in mango ginger root essential oil) IC50=366 μM5[13] ? ?
(+) Isomenthol IC50=100 μM or less[13] ? ?
Ketoconazole ? ? Yes[5]
Milk thistle (contains silybin) [6] ? ? ?
Silybin IC50 92 µM [6] ? ?
Stevioside (a sweetener found in stevia) Strong inhibition [14] ? ?
Valerenic acid IC50 4.96 mM [2] ? ?
Valerian root 84% inhibition [2] ? ?
Methadone ? ? Yes[4][5]

UGT2B15

Inhibitors Strength Dosage Verified in Man
Silybin IC50 75 µM [6] ? ?
Bibliography
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Zhang D, Chando TJ, Everett DW, Patten CJ, Dehal SS, Humphreys WG. PubMed: PMID: 16118329
2. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro.
Alkharfy KM, Frye RF. PubMed: PMID: 17484515
3. Inhibitory effects of commonly used herbal extracts on UDP-glucuronosyltransferase 1A4, 1A6, and 1A9 enzyme activities.
Mohamed ME, Frye RF. PubMed: PMID: 21632963
4. Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects.
Gelston EA, Coller JK, Lopatko OV, James HM, Schmidt H, White JM, Somogyi AA. PubMed: PMID: 22092298
5. In vitro-in vivo extrapolation predicts drug-drug interactions arising from inhibition of codeine glucuronidation by dextropropoxyphene, fluconazole, ketoconazole, and methadone in humans.
Raungrut P, Uchaipichat V, Elliot DJ, Janchawee B, Somogyi AA, Miners JO. PubMed: PMID: 20484152
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Mohamed ME, Frye RF. PubMed: PMID: 21049395
7. Strong inhibition of celastrol towards UDP-glucuronosyl transferase (UGT) 1A6 and 2B7 indicating potential risk of UGT-based herb-drug interaction.
Zhang YS, Tu YY, Gao XC, Yuan J, Li G, Wang L, Deng JP, Wang Q, Ma RM. PubMed: PMID: 22669039
8. Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation.
Lu H, Fang ZZ, Cao YF, Hu CM, Hong M, Sun XY, Li H, Liu Y, Fu X, Sun H. PubMed: PMID: 23237733
9. Deglycosylation of Liquiritin Strongly Enhances its Inhibitory Potential Towards UDP-Glucuronosyltransferase (UGT) Isoforms.
Guo B, Fan XR, Fang ZZ, Cao YF, Hu CM, Yang J, Zhang YY, He RR, Zhu X, Yu ZW, Sun XY, Hong M, Yang L. PubMed: PMID: 23065713
10. Glycyrrhetinic Acid Exhibits Strong Inhibitory Effects Towards UDP-Glucuronosyltransferase (UGT) 1A3 and 2B7.
Huang YP, Cao YF, Fang ZZ, Zhang YY, Hu CM, Sun XY, Yu ZW, Zhu X, Hong M, Yang L, Sun HZ. PubMed: PMID: 23148031
11. Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of 4-methylumbelliferone in human UGT isoforms.
Ismail S, Hanapi NA, Ab Halim MR, Uchaipichat V, Mackenzie PI. PubMed: PMID: 20657500
12. Identification of human UDP-glucuronosyltransferase isoform(s) responsible for the glucuronidation of 2-(4-chlorophenyl)- 5-(2-furyl)-4-oxazoleacetic acid (TA-1801A).
Kaji H, Kume T. PubMed: PMID: 15988124
13. Inhibition of morphine glucuronidation in the liver microsomes of rats and humans by monoterpenoid alcohols.
Ishii Y, Iida N, Miyauchi Y, Mackenzie PI, Yamada H. PubMed: PMID: 22878261
14. Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates.
Wang M, Lu J, Li J, Qi H, Wang Y, Zhang H.; Food Chem Toxicol. 2014 Feb;64:135-43. doi: 10.1016/j.fct.2013.11.028. Epub 2013 Dec 1.; PMID: 24296138; DOI: 10.1016/j.fct.2013.11.028
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