Glucuronidation (Pan troglodytes)

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12Uridine diphosphate glucuronic acid synthesis (co-substrate)Uridine 5'-diphosphateUridine diphosphate glucuronic acidPhosphateNADHPhosphatePGM2WaterGlucose 6-phosphateNADUGP2UGDHUridine triphosphateSubstrateD-GlucoseUGTGlucose 1-phosphateAdenosine 3',5'-diphosphatePGM3PGM1Uridine diphosphate glucosesubstrate-glucuronideAdenosine triphosphate2H+PGM5HK1UGT2B17UGT1A4UGT1A8UGT2A3UGT1A6UGT2B15UGT2B4UGT2B10UGT1A10UGT1A5UGT2A1UGT1A1UGT1A9UGT2B28UGT2A2UGT2B7UGT2B11UGT1A3UGT1A7


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.

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Bibliography

  1. 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
  2. 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

History

View all...
CompareRevisionActionTimeUserComment
106915view13:38, 17 September 2019MaintBotHMDB identifier normalization
87551view02:12, 25 July 2016AlexanderPicoOntology Term : 'classic metabolic pathway' added !
87550view02:12, 25 July 2016AlexanderPicoOntology Term : 'glucuronidation conjugation pathway' added !
69261view18:37, 8 July 2013MaintBotUpdated to 2013 gpml schema
58910view04:48, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
41568view01:59, 2 March 2011MaintBotRemoved redundant pathway information and comments
34296view22:03, 9 December 2009MaintBotAutomatic update of empty xrefs
33521view15:21, 30 November 2009MaintBotRemoved group label
32771view18:33, 4 September 2009MaintBotModified categories
30420view21:16, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2H+MetaboliteHMDB01362 (HMDB)
Adenosine 3',5'-diphosphateMetaboliteHMDB00061 (HMDB)
Adenosine triphosphateMetaboliteHMDB00538 (HMDB)
D-GlucoseMetaboliteHMDB00122 (HMDB)
Glucose 1-phosphateMetaboliteHMDB01586 (HMDB)
Glucose 6-phosphateMetaboliteHMDB01401 (HMDB)
HK1GeneProductENSPTRG00000002572 (Ensembl Chimp)
NADHMetaboliteHMDB01487 (HMDB)
NADMetaboliteHMDB00902 (HMDB)
PGM1GeneProductENSPTRG00000000820 (Ensembl Chimp)
PGM2GeneProductENSPTRG00000015979 (Ensembl Chimp)
PGM3GeneProductENSPTRG00000018379 (Ensembl Chimp)
PGM5GeneProductENSPTRG00000020999 (Ensembl Chimp)
PhosphateMetaboliteHMDB01429 (HMDB)
SubstrateMetabolite
UGDHGeneProductENSPTRG00000015996 (Ensembl Chimp)
UGP2GeneProductENSPTRG00000011976 (Ensembl Chimp)
UGTGeneProduct
UGT1A1GeneProduct
UGT1A10GeneProduct
UGT1A3GeneProduct
UGT1A4GeneProduct
UGT1A5GeneProduct
UGT1A6GeneProduct739942 (Entrez Gene)
UGT1A7GeneProduct
UGT1A8GeneProduct
UGT1A9GeneProduct
UGT2A1GeneProduct742890 (Entrez Gene)
UGT2A2GeneProduct
UGT2A3GeneProduct471220 (Entrez Gene)
UGT2B10GeneProduct461287 (Entrez Gene)
UGT2B11GeneProductENSPTRG00000016110 (Ensembl Chimp)
UGT2B15GeneProduct461289 (Entrez Gene)
UGT2B17GeneProduct743607 (Entrez Gene)
UGT2B28GeneProduct
UGT2B4GeneProduct461285 (Entrez Gene)
UGT2B7GeneProduct471218 (Entrez Gene)
Uridine 5'-diphosphateMetaboliteHMDB00295 (HMDB)
Uridine diphosphate glucoseMetaboliteHMDB00286 (HMDB)
Uridine diphosphate glucuronic acidMetaboliteHMDB00935 (HMDB)
Uridine triphosphateMetaboliteHMDB00285 (HMDB)
WaterMetaboliteHMDB02111 (HMDB)
substrate-glucuronideMetabolite

Annotated Interactions

No annotated interactions
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