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the 21st letter of the Roman alphabet (同)u

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uraniumの化学記号
上流の,上流階級にふさわしい / (映画が)児童観覧用の

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/23 01:47:18」(JST)

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Uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) is a cytosolic glycosyltransferase (EC 2.4.1.17) that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.^[2]

Alternative names:

glucuronyltransferase
UDP-glucuronyl transferase
UDP-GT

Function

Glucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s.

The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances. UGT is present in humans, other animals, plants, and bacteria. Famously, UGT enzymes are not present in the genus Felis,^[3] and this accounts for a number of unusual toxicities in the cat family.

The glucuronidation reaction consists of the transfer of the glucuronosyl group from uridine 5'-diphospho-glucuronic acid (UDPGA) to substrate molecules that contain oxygen, nitrogen, sulfur or carboxyl functional groups.^[4] The resulting glucuronide is more polar (e.g. hydrophilic) and more easily excreted than the substrate molecule. The product solubility in blood is increased allowing it to be eliminated from the body by the kidneys.

Diseases

A deficiency in the bilirubin specific form of glucuronosyltransferase is thought to be the cause of Gilbert's syndrome, which is characterized by unconjugated hyperbilirubinemia.

It is also associated with Crigler-Najjar syndrome, a more serious disorder where the enzyme's activity is either completely absent (Crigler-Najjar syndrome type I) or less than 10% of normal (type II).

Infants may have a developmental deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug chloramphenicol which requires glucuronidation. This leads to a condition known as gray baby syndrome.^[5]

Genes

Human genes which encode UGT enzymes include:

B3GAT1, B3GAT2, B3GAT3
UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10
UGT2A1, UGT2A2, UGT2A3, UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28

References

^ Mulichak AM, Lu W, Losey HC, Walsh CT, Garavito RM (May 2004). "Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands". Biochemistry 43 (18): 5170–5180. doi:10.1021/bi036130c. PMID 15122882.
^ King C, Rios G, Green M, Tephly T (2000). "UDP-glucuronosyltransferases". Curr Drug Metab 1 (2): 143–161. doi:10.2174/1389200003339171. PMID 11465080.
^ Court MH and Greenblatt DJ (2000). "Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms". Pharmacogenetics. 10 (4): 355–69. doi:10.1097/00008571-200006000-00009. PMID 10862526.
^ Bock K, Köhle C (2005). "UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects". Methods Enzymol 400: 57–75. doi:10.1016/S0076-6879(05)00004-2. PMID 16399343.
^ MacDougall, C; Chambers, HF (2011). "55". Protein Synthesis Inhibitors and Miscellaneous Antibacterial Agents. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. (12 ed.). New York: McGraw-Hill. Retrieved October 19, 2011.

External links

Glucuronosyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)

Molecular and Cellular Biology portal

UpToDate Contents

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1. ビリルビン過剰産生によるジルベール症候群および非抱合型ビリルビン過剰産生 gilbert syndrome and unconjugated hyperbilirubinemia due to bilirubin overproduction
2. 成人における抗癌剤の投与 dosing of anticancer agents in adults
3. 新生児における非抱合型高ビリルビン血症の発症機序および病因 pathogenesis and etiology of unconjugated hyperbilirubinemia in the newborn
4. 転移性大腸癌に対する全身化学療法：終了した臨床試験 systemic chemotherapy for metastatic colorectal cancer completed clinical trials
5. ビリルビン代謝 bilirubin metabolism

English Journal

Chiral Inhibition of Rivaroxaban Derivatives Towards UDP-Glucuronosyltransferase (UGT) Isoforms.

Yao Z1, Liu YZ2, Ma AL3, Wang SF2, Lu D4, Hu CM5, Zhang YY6, Wang H7, Hu L8, Deng J3,9, Yang K2, Fang ZZ2.
Chirality.Chirality.2015 Dec;27(12):936-43. doi: 10.1002/chir.22505. Epub 2015 Oct 1.
Rivaroxaban is an oral direct factor Xa (FXa) inhibitor clinically used to prevent and treat thromboembolic disorders. Drug-drug interaction (DDI) exist for rivaroxaban and the inhibitors of CYP3A4/5. This study aims to investigate the inhibition of rivaroxaban and its derivatives with a chiral cent
PMID 26425918

Xenobiotic Metabolism in Mice Lacking the UDP-Glucuronosyltransferase 2 Family.

Fay MJ1, Nguyen MT1, Snouwaert JN1, Dye R1, Grant DJ1, Bodnar WM1, Koller BH2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Dec;43(12):1838-46. doi: 10.1124/dmd.115.065482. Epub 2015 Sep 9.
UDP-Glucuronosyltransferases (UGTs) conjugate a glucuronyl group from glucuronic acid to a wide range of lipophilic substrates to form a hydrophilic glucuronide conjugate. The glucuronide generally has decreased bioactivity and increased water solubility to facilitate excretion. Glucuronidation repr
PMID 26354949

Performance of In Silico Tools for the Evaluation of UGT1A1 Missense Variants.

Rodrigues C1,2, Santos-Silva A1, Costa E1, Bronze-da-Rocha E1.
Human mutation.Hum Mutat.2015 Dec;36(12):1215-25. doi: 10.1002/humu.22903. Epub 2015 Oct 5.
Variations in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) are particularly important because they have been associated with hyperbilirubinemia in Gilbert's and Crigler-Najjar syndromes as well as with changes in drug metabolism. Several variants associated with these p
PMID 26377032

Japanese Journal

Weak activity of UDP-glucuronosyltransferase toward Bisphenol analogs in mouse perinatal development

YABUSAKI Risa,IWANO Hidetomo,TSUAHIMA Sumito,KOIKE Nanako,OHTANI Naoko,TANEMURA Kentaro,INOUE Hiroki,YOKOTA Hiroshi
Journal of Veterinary Medical Science advpub(0), 2015
… BPA is mainly metabolized by UDP-glucuronosyltransferase (UGT), UGT2B1, but this effective metabolizing system is weak in the fetus. …
NAID 130005075577

Tissue distributions of 4-(hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone glucuronide, a stable form of reactive intermediate produced from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, in the rat

Nishiyama Takahito,Ogura Kenichiro,Ohnuma Tomokazu [他]
The Journal of toxicological sciences : an official journal of the Japanese Society of Toxicology 39(2), 263-267, 2014-04
NAID 40020063592

Effect of Adrenalectomy on Expression and Induction of UDP-Glucuronosyltransferase 1A6 and 1A7 in Rats

Sakakibara Yukiko,Katoh Miki,Suzuki Masaya [他]
Biological & pharmaceutical bulletin 37(4), 618-624, 2014-04
NAID 40020030196

Related Pictures

Human UGT1A1/UDP-glucuronosyltransferase 1-1 ELISA Kit | ELISA Genie Glucuronosyltransferase; Glucuronyltransferase; UDP Glucuronosyltransferase Human UDP-Glucuronosyltransferase Isoforms Involved in Haloperidol Glucuronidation and Rat (Rattus) UGT1A1 ELISA Kit | Product No. ABIN3168761 Epirubicin Glucuronidation Is Catalyzed by Human UDP-Glucuronosyltransferase 2B7 Modulation of Irinotecan-induced Diarrhea by Cotreatment with Neomycin in Cancer Frontiers | The UDP-glucuronosyltransferases of the blood-brain barrier: their role in Glucuronidation of Antiallergic Drug, Tranilast: Identification of Human UDP

★リンクテーブル★

リンク元	「薬物代謝」「UDP-グルクロノシルトランスフェラーゼ」「ビリルビンジグルクロニド」
関連記事	「glucuronosyltransferase」「UDP」「U」

「薬物代謝」

UDP-glucuronosyl and UDP-glucosyl transferase
	Structure of TDP-vancosaminyltransferase GtfD as a complex with TDP and the natural substrate, desvancosaminyl vancomycin.
Identifiers
Symbol	UDPGT
Pfam	PF00201
InterPro	IPR002213
PROSITE	PDOC00359
SCOP	1rrv
SUPERFAMILY	1rrv
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Search
PMC	articles
PubMed	articles
NCBI	proteins

Glucuronosyltransferase
Identifiers
EC number	2.4.1.17
CAS number	9030-08-4
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: drug metabolism
関

肝臓が貢献。例外的に肺や腎で代謝されることもある

薬物代謝の過程

1. 第1相反応：酸化oxidation、還元reduction、加水分解hydrolysis

oxygenases

-OH, -COOH, SH, -O=, -NH2を付与

生物学的性質の不活化

2. 第2相反応：抱合conjugation

transerases

可溶化。分子量の増加→腎排泄されやすくなる

生物異物代謝 (GOO.73)

ENZYMES					反応
Phase 1	oxygenases	シトクロムP450	cytochrome P450	CYP	C, Oの酸化。脱アルキル化
		フラビン含有モノオキシゲナーゼ	flavin-containing monooxygenase	FMO	N,S,Pの酸化
		エポキシドヒドラーゼ(mEH, sEH)	epoxide hydrolases	mEH, sEH	エポキシドの加水分解
Phase 2	transferases?	スルホトランスフェラーゼ	sulfotransferase	SULT	硫酸の
		UDP-グルクロノシルトランスフェラーゼ	UDP-glucuronosyltransferase	UGT	グルクロン酸の付加
		グルタチオンS-トランスフェラーゼ	glutathione-S-transferase	GST	グルタチオンの付加
		N-アセチルトランスフェラーゼ	N-acetyltransferase	NAT	アセチル基の付加
		メチルトランスフェラーゼ	methyltransferase	MT	メチル基の付加
Other enzymes?		アルコール脱水素酵素	alcohol dehydrogenases	ADH	アルコールの還元
		アルデヒド脱水素酵素	aldehyde dehydrogenases	ALDH	アルデヒドの還元
		NADPH/キノン酸化還元酵素	NADPH-quinone oxidoreductase	NQO	キノンの還元