Glucuronidation (WP698)

Homo sapiens

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 [https://assays.cancer.gov/available_assays?wp_id=WP698 CPTAC Assay Portal]

Authors

Pieter Giesbertz , Alex Pico , Egon Willighagen , Denise Slenter , Kristina Hanspers , and Eric Weitz

Activity

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Organisms

Homo sapiens

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:ENSG00000169764
PGM3 GeneProduct ensembl:ENSG00000013375
PGM5 GeneProduct ensembl:ENSG00000154330
PGM2 GeneProduct ensembl:ENSG00000169299
HK1 GeneProduct ensembl:ENSG00000156515
UGDH GeneProduct ensembl:ENSG00000109814
PGM1 GeneProduct ensembl:ENSG00000079739
UGT2B17 GeneProduct ncbigene:7367
UGT1A4 GeneProduct ncbigene:54657
UGT1A8 GeneProduct ncbigene:54576
UGT2A3 GeneProduct ncbigene:79799
UGT1A6 GeneProduct ncbigene:54578
UGT2B15 GeneProduct ncbigene:7366
UGT2B4 GeneProduct ncbigene:7363
UGT2B10 GeneProduct ncbigene:7365
UGT1A10 GeneProduct ncbigene:54575
UGT1A5 GeneProduct ncbigene:54579
UGT2A1 GeneProduct ncbigene:10941
UGT1A1 GeneProduct ncbigene:54658
UGT1A9 GeneProduct ncbigene:54600
UGT2B28 GeneProduct ncbigene:54490
UGT2A2 GeneProduct ncbigene:574537
UGT2B7 GeneProduct ncbigene:7364
UGT2B11 GeneProduct ensembl:ENSG00000213759
UGT1A3 GeneProduct ncbigene:54659
UGT1A7 GeneProduct ncbigene:54577

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