Glucuronidation (WP1276)

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.
last edited

Authors

MaintBot, Christine Chichester, and Egonw

Cited In

Organism

Rattus norvegicus

Communities

Annotations

Pathway Ontology: glucuronidation conjugation pathway

Participants

Label Type Compact Identifier
Adenosine 3,5-diphosphate Metabolite hmdb:HMDB0000061
2H+ Metabolite chebi:15378
Ugp2 GeneProduct ensembl:ENSRNOG00000008079
Glucose 6-phosphate Metabolite hmdb:HMDB0001401
UGT GeneProduct None
Substrate Metabolite None
NP_001102242.1 GeneProduct ensembl:ENSRNOG00000009515
PGM5 GeneProduct ncbigene:679990
Pgm2 GeneProduct ensembl:ENSRNOG00000002185
Uridine 5-diphosphate Metabolite HMDB
substrate-glucuronide Metabolite None
NAD Metabolite HMDB
Water Metabolite HMDB
Adenosine triphosphate Metabolite HMDB
NADH Metabolite HMDB
HK1 GeneProduct Entrez Gene
Uridine diphosphate glucose Metabolite HMDB
Phosphate Metabolite HMDB
Ugdh GeneProduct Ensembl
Glucose 1-phosphate Metabolite HMDB
Uridine diphosphate glucuronic acid Metabolite HMDB
Phosphate Metabolite HMDB
Uridine triphosphate Metabolite HMDB
D-Glucose Metabolite HMDB
Pgm1 GeneProduct Ensembl
UGT2B17 GeneProduct Entrez Gene
Ugt1a5 GeneProduct Entrez Gene
UGT1A8 GeneProduct Entrez Gene
Ugt2a3 GeneProduct Entrez Gene
Ugt1a6 GeneProduct Entrez Gene
Ugt2b36 GeneProduct Entrez Gene
Ugt2b17 GeneProduct Entrez Gene
Ugt2b34 GeneProduct Entrez Gene
UGT1A10 GeneProduct None
Ugt1a3 GeneProduct Entrez Gene
Ugt2a1 GeneProduct Entrez Gene
Ugt1a1 GeneProduct Entrez Gene
UGT1A9 GeneProduct Entrez Gene
UGT2B28 GeneProduct None
UGT2A2 GeneProduct None
LOC286989 GeneProduct Entrez Gene
UGT2B11 GeneProduct None
Ugt1a2 GeneProduct Entrez Gene
UGT1A7 GeneProduct None
None

References

  1. Testa B, Krämer SD. The biochemistry of drug metabolism--an introduction: part 4. reactions of conjugation and their enzymes. Chem Biodivers. 2008 Nov;5(11):2171–336. 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 Mar 15;69(6):2332–9. PubMed Europe PMC Scholia