Glucuronidation (Homo sapiens)

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12Substrate-glucoronideSubstratePGM1HK1NADHUGP2Uridine 5'-diphosphateAdenosine triphosphateUridine diphosphate glucuronic acidPGM2Adenosine 3',5'-diphosphateGlucose 6-phosphatePGM3PhosphateGlucose 1-phosphatePGM5WaterUridine diphosphate glucoseUridine triphosphatePhosphate2H+D-GlucoseNADUGDHUGT2B17UGT1A4UGT1A8UGT2A3UGT1A6UGT2B15UGT2B4UGT2B10UGT1A10UGT1A5UGT2A1UGT1A1UGT1A9UGT2B28UGT2A2UGT2B7UGT2B11UGT1A3UGT1A7


Description

Metabolism of xenobiotic compounds consists of phase I and a phase II biotransformation reactions, being compound modification and conjugation reactions respectively. In phase I biotransformation, the compound is modificated via oxidation, reduction, hydrolysis, or other minor reactions, to reveal a reactive group to which a conjugation molecule can react to. In phase II, a small conjugation molecule reacts with the phase I modified molecule, producing a much more water-soluble molecule that can be excreted more easily.

Glucuronidation is a phase II biotransformation reaction in which glucuronide acts as a conjugation molecule and binds to a substrate via the catalysis of glucuronosyltransferases. First, in a series of reactions the cosubstrate uridine diphosphate glucuronic acid (UDPGA) is formed. The glucuronosyltransferases (UGTs) then catalyze the transfer of glucuronic acid from UDPGA to a substrate resulting in a glucuronidated substrate and leaving uridine 5'-diphosphate. UGTs are a very broad and divers group of enzymes and count as the most significant group of conjugation enzymes in xenobiotic metabolism, qualitatively because glucuronic acid can be coupled to a large diversity of functional groups and quantitatively because of the large and divers number of substrates that are formed.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Bibliography

  1. Testa B, Kramer SD; ''The biochemistry of drug metabolism--an introduction: part 4. reactions of conjugation and their enzymes.''; Chem Biodivers, 2008 PubMed Europe PMC Scholia
  2. Wei Q, Galbenus R, Raza A, Cerny RL, Simpson MA; ''Androgen-stimulated UDP-glucose dehydrogenase expression limits prostate androgen availability without impacting hyaluronan levels.''; Cancer Res, 2009 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134404view20:26, 21 July 2024EweitzIncrease contrast for readability, standardize case
126233view09:43, 17 April 2023EgonwLicense is CCZero
106827view13:30, 17 September 2019MaintBotHMDB identifier normalization
106433view23:23, 28 August 2019KhanspersModified description
105609view04:53, 10 August 2019KhanspersModified description
94183view13:53, 25 August 2017DeSlChanged two metabolite nodes to text labels, since they are not metabolite nodes.
79224view13:50, 15 March 2015EgonwReplaced the HMDB H2 identifier with H+ from ChEBI.
63198view20:54, 8 May 2013MaintBotUpdating gpml version
59087view22:07, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
45317view20:08, 7 October 2011AlexanderPicoOntology Term : 'glucuronidation conjugation pathway' added !
45315view20:07, 7 October 2011AlexanderPicocleaner visual semantics
41030view23:15, 1 March 2011MaintBotRemoved redundant pathway information and comments
38927view21:34, 24 September 2010AlexanderPicoconverted complexes to groups
33413view14:50, 30 November 2009MaintBotRemoved group label
32741view23:15, 3 September 2009MaintBotModified categories
30281view00:34, 26 July 2009AlexanderPicoReverted to version '13:07, 25 July 2009' by AlexanderPico
30278view21:06, 25 July 2009AlexanderPicofixing apostrophes
30277view20:59, 25 July 2009AlexanderPicofixing apostrophes
30266view20:07, 25 July 2009AlexanderPicofixed unsupported characters in bibliography
30021view09:06, 26 June 2009Pieter GiesbertzCorrected datanode error
29859view08:46, 8 June 2009Pieter GiesbertzModified description
29858view08:38, 8 June 2009Pieter GiesbertzModified description
29667view12:17, 25 May 2009Pieter GiesbertzRemoved literature reference
29666view12:16, 25 May 2009Pieter GiesbertzSpecify description
29657view11:15, 24 May 2009Pieter GiesbertzAdded literature references
29326view10:12, 24 April 2009Pieter GiesbertzSpecify description
29285view07:48, 22 April 2009Pieter GiesbertzSpecify description
29263view08:59, 21 April 2009Pieter GiesbertzSpecify description
29235view08:18, 17 April 2009Pieter GiesbertzSpecify description
29233view14:19, 16 April 2009Pieter GiesbertzSpecify description
29232view14:13, 16 April 2009Pieter GiesbertzSpecify description
29231view13:45, 16 April 2009Pieter GiesbertzPeriodical save, work in progress
29230view12:19, 16 April 2009Pieter GiesbertzNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2H+MetaboliteCHEBI:15378 (ChEBI)
Adenosine 3',5'-diphosphateMetaboliteHMDB0000061 (HMDB)
Adenosine triphosphateMetaboliteHMDB0000538 (HMDB)
D-GlucoseMetaboliteHMDB0000122 (HMDB)
Glucose 1-phosphateMetaboliteHMDB0001586 (HMDB)
Glucose 6-phosphateMetaboliteHMDB0001401 (HMDB)
HK1GeneProductENSG00000156515 (Ensembl)
NADHMetaboliteHMDB0001487 (HMDB)
NADMetaboliteHMDB0000902 (HMDB)
PGM1GeneProductENSG00000079739 (Ensembl)
PGM2GeneProductENSG00000169299 (Ensembl)
PGM3GeneProductENSG00000013375 (Ensembl)
PGM5GeneProductENSG00000154330 (Ensembl)
PhosphateMetaboliteHMDB0001429 (HMDB)
UGDHGeneProductENSG00000109814 (Ensembl)
UGP2GeneProductENSG00000169764 (Ensembl)
UGT1A10GeneProduct54575 (Entrez Gene)
UGT1A1GeneProduct54658 (Entrez Gene)
UGT1A3GeneProduct54659 (Entrez Gene)
UGT1A4GeneProduct54657 (Entrez Gene)
UGT1A5GeneProduct54579 (Entrez Gene)
UGT1A6GeneProduct54578 (Entrez Gene)
UGT1A7GeneProduct54577 (Entrez Gene)
UGT1A8GeneProduct54576 (Entrez Gene)
UGT1A9GeneProduct54600 (Entrez Gene)
UGT2A1GeneProduct10941 (Entrez Gene)
UGT2A2GeneProduct574537 (Entrez Gene)
UGT2A3GeneProduct79799 (Entrez Gene)
UGT2B10GeneProduct7365 (Entrez Gene)
UGT2B11GeneProductENSG00000213759 (Ensembl)
UGT2B15GeneProduct7366 (Entrez Gene)
UGT2B17GeneProduct7367 (Entrez Gene)
UGT2B28GeneProduct54490 (Entrez Gene)
UGT2B4GeneProduct7363 (Entrez Gene)
UGT2B7GeneProduct7364 (Entrez Gene)
Uridine 5'-diphosphateMetaboliteHMDB0000295 (HMDB)
Uridine diphosphate glucoseMetaboliteHMDB0000286 (HMDB)
Uridine diphosphate glucuronic acidMetaboliteHMDB0000935 (HMDB)
Uridine triphosphateMetaboliteHMDB0000285 (HMDB)
WaterMetaboliteHMDB0002111 (HMDB)

Annotated Interactions

No annotated interactions

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