Recombinant Human UDP-glucuronosyltransferase 2B10 (UGT2B10)
Description
Introduction to Recombinant Human UDP-glucuronosyltransferase 2B10 (UGT2B10)
Recombinant Human UDP-glucuronosyltransferase 2B10 (UGT2B10) is a protein-coding gene product that plays a crucial role in the metabolism of various drugs and endogenous compounds through glucuronidation. This enzyme belongs to the UDP-glucuronosyltransferase family, which is essential for conjugating glucuronic acid to lipophilic substances, thereby enhancing their solubility and facilitating their excretion from the body.
Function and Localization
UGT2B10 is primarily involved in the N-glucuronidation of tertiary amines, including several drugs and endogenous compounds. It is located in the endoplasmic reticulum membrane and is an integral component of intracellular membrane-bounded organelles . The enzyme is mainly expressed in the liver, where it contributes to the detoxification of xenobiotics and endogenous substances.
Substrate Specificity
UGT2B10 has been identified as a catalyst for the glucuronidation of various substrates, including:
-
Antidepressants and antipsychotics: Such as cyclobenzaprine, mirtazapine, and clozapine .
-
Tobacco-related nitrosamines: Highlighting its role in detoxifying carcinogenic compounds .
Research Findings
Recent studies have explored the role of UGT2B10 in drug metabolism, particularly in the context of hematopoietic stem cell transplantation (HSCT) and its potential involvement in sinusoidal occlusion syndrome (SOS) . Additionally, UGT2B10 has been implicated in the metabolism of lamotrigine, an anticonvulsant drug, alongside UGT1A4 .
Table 1: Substrates and Ligands of UGT2B10
| Substrate/Ligand | Binding Energy (ΔG) [kcal/mol] | Dissociation Constant (Kd) [mM] |
|---|---|---|
| Amitriptyline | -1.9 ± 0.2 | 39.0 |
| Itraconazole | 19.0 ± 0.5 | 1.1 × 10^17 |
| 4-hydroxy voriconazole | -1.0 ± 0.0 | 184.7 |
| Acetaminophen | -5.5 ± 0.0 | 0.1 |
| Cyclosporine A | 154.9 ± 2.9 | 1.8 × 10^118 |
| Bilirubine | 6.9 ± 0.0 | 1.2 × 10^15 |
| Dihydroxy voriconazole | -0.6 ± 0.0 | 363.0 |
| Hydroxy voriconazole | -1.2 ± 0.1 | 125.0 |
| Lorazepam | -2.6 ± 0.0 | 12.4 |
| Methotrexate | -0.5 ± 0.5 | 567.3 |
Genetic Variants and Disease Association
Genetic variants in the UGT2B10 gene have been associated with altered drug metabolism and may influence the risk of certain conditions, such as sinusoidal occlusion syndrome following HSCT . Additionally, UGT2B10 is linked to diseases like Crigler-Najjar Syndrome and Gilbert Syndrome, although its direct role in these conditions is less clear .
Product Specs
Note: While we prioritize shipping the format currently in stock, please specify your format preference in order notes for customized preparation.
Note: All proteins are shipped with standard blue ice packs unless dry ice is specifically requested in advance. Additional fees apply for dry ice shipping.
The tag type will be determined during production. If you require a specific tag, please inform us, and we will prioritize its development.
Target Background
- UGT2B10 was initially identified as an N-glucosidation enzyme. The generated N-glucosides are primarily excreted via the BCRP transporter. PMID: 29691239
- Androgens significantly contribute to the regulation of UGT2B10 expression in the liver. PMID: 29438977
- UGT2B10 activity or genotype should be considered when using cotinine as a tobacco exposure biomarker, particularly in populations like African Americans with high frequencies of UGT2B10 nonfunctional variants. PMID: 28264876
- Spatial features influence the potency of UGT2B10 inhibition. PMID: 26669329
- Carriers of UGT2B10 variant alleles exhibited increased C-oxidation levels (P = 0.0099). All metabolic pathways should be considered when assessing the role of nicotine metabolism in smoking behavior and cancer risk. PMID: 25233931
- CYP2A6 and UGT2B10 genotypes explain 53% of the variance in oral nicotine glucuronidation and are significantly associated with undeuterated (D0) nicotine glucuronidation in ad libitum smokers. PMID: 24192532
- Studies highlight the substrate specificity of UGT2B10, demonstrating its preference for tertiary amines with higher affinities and clearance values compared to UGT1A4 and UGT1A3. PMID: 23611809
- UGT2B17 and UGT2B10 are key enzymes in 3HC glucuronidation in the human liver. Functional polymorphisms in these genes are associated with significantly reduced 3HC glucuronidation activities. PMID: 22228205
- UGT2B10 predicts metabolic disease (MD) independently of age, hormone therapy, and parity. PMID: 20799965
- UGT2B10 and UGT2B17 play crucial roles in nicotine glucuronidation. The UGT2B10 codon 67 SNP and UGT2B17 gene deletion reduce overall glucuronidation rates of nicotine and its metabolites in smokers. PMID: 20876810
- UGT2B10 genotype influences nicotine metabolism and should be considered when characterizing its role in smoking behavior. PMID: 20501767
- Research reports on nicotine glucuronidation and UGT2B10. PMID: 17576790
- UGT2B10 is a major hepatic enzyme in nicotine/cotinine glucuronidation. The UGT2B10*2 variant reduces nicotine- and cotinine-N-glucuronidation, influencing nicotine metabolism and elimination. PMID: 17909004
- The UGT2B10(67Tyr) variant (haplotype C) is a functional SNP that may affect interindividual variation in NNAL-N-glucuronidation activity and potentially increase susceptibility to smoking-related cancers. PMID: 18300939
