Glucuronidation (WP1241)

Mus musculus

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.

Authors

Christine Chichester and Egon Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Mus musculus

Communities

Annotations

Pathway Ontology

glucuronidation conjugation pathway

Participants

Label Type Compact URI Comment
Adenosine 3',5'-diphosphate Metabolite hmdb:HMDB0000061
2H+ Metabolite chebi:15378
Glucose 6-phosphate Metabolite hmdb:HMDB0001401
Uridine 5'-diphosphate Metabolite hmdb:HMDB0000295
NAD Metabolite hmdb:HMDB0000902
Water Metabolite hmdb:HMDB0002111
Adenosine triphosphate Metabolite hmdb:HMDB0000538
NADH Metabolite hmdb:HMDB0001487
Uridine diphosphate glucose Metabolite hmdb:HMDB0000286
Phosphate Metabolite hmdb:HMDB0001429
Glucose 1-phosphate Metabolite hmdb:HMDB0001586
Uridine diphosphate glucuronic acid Metabolite hmdb:HMDB0000935
Uridine triphosphate Metabolite hmdb:HMDB0000285
D-Glucose Metabolite hmdb:HMDB0000122
Ugp2 GeneProduct ensembl:ENSMUSG00000001891
Pgm3 GeneProduct ensembl:ENSMUSG00000056131
PGM5 GeneProduct ncbigene:226041
Pgm1 GeneProduct ensembl:ENSMUSG00000029171
Hk1 GeneProduct ensembl:ENSMUSG00000037012
Ugdh GeneProduct ensembl:ENSMUSG00000029201
Pgm2 GeneProduct ensembl:ENSMUSG00000025791
Ugt1a5 GeneProduct ncbigene:394433
Ugt1a8 GeneProduct mgi:MGI:3576090
Ugt2a3 GeneProduct ncbigene:72094
Ugt2b1 GeneProduct ncbigene:71773
Ugt2b34 GeneProduct ncbigene:100727
Ugt1a10 GeneProduct ncbigene:394430
Ugt2a1 GeneProduct ncbigene:94215
Ugt1a1 GeneProduct ncbigene:394436
Ugt1a9 GeneProduct ncbigene:434493
Ugt2a2 GeneProduct ncbigene:552899
Ugt1a2 GeneProduct ncbigene:22236

References

  1. The biochemistry of drug metabolism--an introduction: part 4. reactions of conjugation and their enzymes. Testa B, Krämer SD. Chem Biodivers. 2008 Nov;5(11):2171–336. PubMed Europe PMC Scholia
  2. Androgen-stimulated UDP-glucose dehydrogenase expression limits prostate androgen availability without impacting hyaluronan levels. Wei Q, Galbenus R, Raza A, Cerny RL, Simpson MA. Cancer Res. 2009 Mar 15;69(6):2332–9. PubMed Europe PMC Scholia