UDP-glucuronosyltransferase and UDP-glucose dehydrogenase (UGT/UGDH)

UDP-glucuronosyltransferases (UGTs) and UDP-glucose dehydrogenase (UGDH) constitute a critical metabolic axis responsible for the glucuronidation pathway [PMID: 15507121]. UGDH is a cytosolic enzyme that catalyzes the rate-limiting step in the production of UDP-glucuronic acid, the essential sugar donor, by oxidizing UDP-glucose [UniProt O14773]. UGTs are membrane-bound enzymes located in the endoplasmic reticulum that conjugate this glucuronic acid to a wide variety of endogenous (e.g., bilirubin, steroid hormones) and exogenous (e.g., drugs, environmental toxins) compounds [PMID: 10769175]. This process increases the water solubility of these molecules, facilitating their excretion via bile or urine. Dysregulation or genetic polymorphisms in these enzymes, particularly UGT1A1, are linked to conditions like Gilbert syndrome and significant variations in drug toxicity and efficacy, such as the dose-limiting neutropenia seen with the chemotherapeutic irinotecan [PMID: 15996205]. Additionally, UGDH plays a role in the synthesis of glycosaminoglycans, linking this pathway to cellular signaling and cancer progression [PMID: 28630105].

Other names

UDP-glucuronosyltransferase (UGT)UDP-glucose 6-dehydrogenase (UGDH)UDP-glucuronosyltransferase familyGlucuronosyltransferaseGlucuronidation pathway enzymes

The pathway functions through the UGDH-catalyzed oxidation of UDP-glucose to UDP-glucuronic acid, which then serves as the essential cofactor for UGT-mediated conjugation of lipophilic substrates, facilitating their detoxification and renal or biliary excretion [PMID: 15507121, UniProt O14773].