UGT2B7

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UDP glucuronosyltransferase 2 family, polypeptide B7
PDB 2o6l EBI.png
PDB rendering based on 2o6l.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols UGT2B7 ; UDPGT 2B9; UDPGT2B7; UDPGTH2; UGT2B9
External IDs OMIM600068 HomoloGene128251 ChEMBL: 4370 GeneCards: UGT2B7 Gene
EC number 2.4.1.17
Orthologs
Species Human Mouse
Entrez 7364 231396
Ensembl ENSG00000171234 ENSMUSG00000070704
UniProt P16662 n/a
RefSeq (mRNA) NM_001074 NM_001029867
RefSeq (protein) NP_001065 NP_001025038
Location (UCSC) Chr 4:
69.92 – 69.98 Mb
Chr 5:
87.07 – 87.09 Mb
PubMed search [1] [2]

UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltransferase-2B7 is encoded by the UGT2B7 gene.[1][2]

Function[edit]

The UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. UGT2B7 has unique specificity for 3,4-catechol estrogens and estriol, suggesting that it may play an important role in regulating the level and activity of these potent estrogen metabolites.

This enzyme is located on the endoplasmic reticulum and nuclear membranes of cells. Its function is to catalyse the conjugation of a wide variety of lipophilic aglycon substrates with glucuronic acid, using uridine diphosphate glucuronic acid.

Together with UGT2B4, UGT2B7 is capable of glucosidation of hyodesoxycholic acid in the liver, but, unlike the 2B4 isoform, 2B7 is also able to glucuronidate various steroid hormones (androsterone, epitestosterone) and fatty acids.[3][4] It is also able to conjugate major classes of drugs such as analgesics (morphine), carboxylic nonsteroidal anti-inflammatory drugs (ketoprofen), and anticarcinogens (all-trans retinoic acid).[4] UGT2B7 is the major enzyme isoform for the metabolism of morphine to the main metabolites, morphine-3-glucuronide (M3G) which has no analgesic effect and morphine-6-glucuronide (M6G),[5] which has analgesic effects less potent than morphine.[6] As a consequence, altered UGT2B7 activity can significantly affect both the effectiveness and side-effects of morphine, as well as some related opiate drugs.[7][8][9][10][11]

References[edit]

  1. ^ Ritter JK, Sheen YY, Owens IS (May 1990). "Cloning and expression of human liver UDP-glucuronosyltransferase in COS-1 cells. 3,4-catechol estrogens and estriol as primary substrates". J. Biol. Chem. 265 (14): 7900–6. PMID 2159463. 
  2. ^ Monaghan G, Clarke DJ, Povey S, See CG, Boxer M, Burchell B (September 1994). "Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4q13". Genomics 23 (2): 496–9. doi:10.1006/geno.1994.1531. PMID 7835904. 
  3. ^ Mackenzie P, Little JM, Radominska-Pandya A (February 2003). "Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7". Biochem. Pharmacol. 65 (3): 417–21. doi:10.1016/S0006-2952(02)01522-8. PMID 12527334. 
  4. ^ a b Barre L, Fournel-Gigleux S, Finel M, Netter P, Magdalou J, Ouzzine M (March 2007). "Substrate specificity of the human UDP-glucuronosyltransferase UGT2B4 and UGT2B7. Identification of a critical aromatic amino acid residue at position 33". FEBS J. 274 (5): 1256–64. doi:10.1111/j.1742-4658.2007.05670.x. PMID 17263731. 
  5. ^ Coffman B, Rios G, King C, Tephly T (1 January 1997). "Human UGT2B7 catalyzes morphine glucuronidation". Drug Metab. Dispos. 25 (1): 1–4. PMID 9010622. 
  6. ^ van Dorp EL, Romberg R, Sarton E, Bovill JG, Dahan A (2006). "Morphine-6-glucuronide: morphine's successor for postoperative pain relief?". Anesthesia and Analgesia 102 (6): 1789–1797. doi:10.1213/01.ane.0000217197.96784.c3. PMID 16717327. 
  7. ^ Coller, JK; Christrup, LL; Somogyi, AA (2009). "Role of active metabolites in the use of opioids.". European journal of clinical pharmacology 65 (2): 121–39. doi:10.1007/s00228-008-0570-y. PMID 18958460. 
  8. ^ Fujita, KI; Ando, Y; Yamamoto, W; Miya, T; Endo, H; Sunakawa, Y; Araki, K; Kodama, K; Nagashima, F (2009). "Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer". Cancer chemotherapy and pharmacology 65 (2): 251–8. doi:10.1007/s00280-009-1029-2. PMID 19466410. 
  9. ^ Abildskov, K; Weldy, P; Garland, M (2010). "Molecular Cloning of the Baboon UDP-Glucuronosyltransferase 2B Gene Family and Their Activity in Conjugating Morphine". Drug metabolism and disposition: the biological fate of chemicals 38 (4): 545–53. doi:10.1124/dmd.109.030635. PMC 2845934. PMID 20071451. 
  10. ^ Pergolizzi, JV; Raffa, RB; Gould, E (2009). "Considerations on the use of oxymorphone in geriatric patients". Expert opinion on drug safety 8 (5): 603–13. doi:10.1517/14740330903153854. PMID 19614559. 
  11. ^ Rouguieg, K; Picard, N; Sauvage, FL; Gaulier, JM; Marquet, P (2010). "Contribution of the different UDP-glucuronosyltransferase (UGT) isoforms to buprenorphine and norbuprenorphine metabolism and relationship with the main UGT polymorphisms in a bank of human liver microsomes". Drug metabolism and disposition: the biological fate of chemicals 38 (1): 40–5. doi:10.1124/dmd.109.029546. PMID 19841060. 

Further reading[edit]

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