Glucuronidation (Rattus norvegicus)

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12Uridine diphosphate glucuronic acid synthesis (co-substrate)Glucose 1-phosphatesubstrate-glucuronideUridine 5'-diphosphateSubstratePgm2HK1UGTAdenosine 3',5'-diphosphateUridine triphosphate2H+Ugp2WaterNADHGlucose 6-phosphatePGM5NADUridine diphosphate glucuronic acidPgm1PhosphateUridine diphosphate glucosePhosphateD-GlucoseUgdhNP_001102242.1Adenosine triphosphateUGT2B17Ugt1a5UGT1A8Ugt2a3Ugt1a6Ugt2b36Ugt2b17Ugt2b34UGT1A10Ugt1a3Ugt2a1Ugt1a1UGT1A9UGT2B28UGT2A2LOC286989UGT2B11Ugt1a2UGT1A7


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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP698(r30281) with a 59% conversion rate.

Quality Tags

Ontology Terms

 

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
  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

History

View all...
CompareRevisionActionTimeUserComment
106947view13:41, 17 September 2019MaintBotHMDB identifier normalization
79225view13:55, 15 March 2015EgonwReplaced the HMDB H2 identifier with H+ from ChEBI.
69443view19:05, 8 July 2013MaintBotUpdated to 2013 gpml schema
67289view10:32, 26 June 2013Christine ChichesterOntology Term : 'glucuronidation conjugation pathway' added !
58970view18:45, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
41769view02:41, 2 March 2011MaintBotRemoved redundant pathway information and comments
34137view19:32, 9 December 2009MaintBotAutomatic update of empty xrefs
32755view23:36, 3 September 2009MaintBotModified categories
31876view12:39, 14 August 2009MaintBotFixed group labels
30919view00:33, 30 July 2009MaintBotNew 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)
HK1GeneProduct25058 (Entrez Gene)
LOC286989GeneProduct286989 (Entrez Gene)
NADHMetaboliteHMDB0001487 (HMDB)
NADMetaboliteHMDB0000902 (HMDB)
NP_001102242.1GeneProductENSRNOG00000009515 (Ensembl)
PGM5GeneProduct679990 (Entrez Gene)
Pgm1GeneProductENSRNOG00000009889 (Ensembl)
Pgm2GeneProductENSRNOG00000002185 (Ensembl)
PhosphateMetaboliteHMDB0001429 (HMDB)
SubstrateMetabolite
UGTGeneProduct
UGT1A10GeneProduct
UGT1A7GeneProduct
UGT1A8GeneProduct301595 (Entrez Gene)
UGT1A9GeneProduct396552 (Entrez Gene)
UGT2A2GeneProduct
UGT2B11GeneProduct
UGT2B17GeneProduct286954 (Entrez Gene)
UGT2B28GeneProduct
UgdhGeneProductENSRNOG00000002643 (Ensembl)
Ugp2GeneProductENSRNOG00000008079 (Ensembl)
Ugt1a1GeneProduct24861 (Entrez Gene)
Ugt1a2GeneProduct396527 (Entrez Gene)
Ugt1a3GeneProduct396551 (Entrez Gene)
Ugt1a5GeneProduct574523 (Entrez Gene)
Ugt1a6GeneProduct113992 (Entrez Gene)
Ugt2a1GeneProduct63867 (Entrez Gene)
Ugt2a3GeneProduct289533 (Entrez Gene)
Ugt2b17GeneProduct286954 (Entrez Gene)
Ugt2b34GeneProduct305264 (Entrez Gene)
Ugt2b36GeneProduct83808 (Entrez Gene)
Uridine 5'-diphosphateMetaboliteHMDB0000295 (HMDB)
Uridine diphosphate glucoseMetaboliteHMDB0000286 (HMDB)
Uridine diphosphate glucuronic acidMetaboliteHMDB0000935 (HMDB)
Uridine triphosphateMetaboliteHMDB0000285 (HMDB)
WaterMetaboliteHMDB0002111 (HMDB)
substrate-glucuronideMetabolite

Annotated Interactions

No annotated interactions
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