- Catalog No: MBE-0007
- Species: Human
- Source: ExpiSf9™ Cells
- Substrates: Steroids/Bilirubin/Hormones/Lipophilic Molecules or others
- Overview:
- UGT1A8, formally known as UDP-Glucuronosyltransferase 1A8, belongs to the UDP-glucuronosyltransferase (UGT) superfamily, a group of enzymes that play a pivotal role in phase II metabolism. This enzyme specifically catalyzes the glucuronidation of various lipophilic molecules, transforming them into water-soluble, excretable metabolites. UGT1A8 is involved in the metabolism of a wide range of substrates, including steroids, bilirubin, hormones, and drugs, making it a crucial player in the elimination and detoxification of these compounds from the body.
Key Features of UGT1A8:
Enzymatic Activity:
UGT1A8 encodes a UDP-glucuronosyltransferase, an enzyme that conjugates small lipophilic molecules with glucuronic acid, enhancing their water solubility and promoting excretion through urine or bile. This process is essential for the elimination of drugs, toxins, and endogenous compounds.
The enzyme exhibits a broad substrate specificity, catalyzing the glucuronidation of compounds such as steroids, hormones, bilirubin, and various drugs.
Genetic Complexity:
The UGT1A8 gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. This locus includes multiple alternate first exons and common exons, resulting in various protein isoforms with distinct N-termini but identical C-termini.
Each first exon encodes the substrate binding site and is regulated by its own promoter, contributing to the enzyme’s diverse substrate specificity.
Structural and Functional Characteristics:
UGT1A8 protein, with a full length of 505 amino acids and a molecular weight of 59.9 kDa, is a recombinant protein commonly expressed in cell-free systems such as E. coli.
The enzyme has glucuronidase activity with many substrates, including coumarins, phenols, anthraquinones, flavones, and some opioids.
- Application in Drug Development:
- Drug Metabolism Prediction and Optimization:
- UGT1A8 plays a significant role in the metabolism of numerous drugs, making it a crucial factor in predicting drug pharmacokinetics. By studying the interaction between UGT1A8 and drug candidates, researchers can optimize drug dosing regimens and predict potential drug-drug interactions.
The enzyme’s broad substrate specificity allows it to metabolize a wide range of drugs, including some with narrow therapeutic indices, highlighting its importance in ensuring safe and effective drug therapy.
- UGT1A8 plays a significant role in the metabolism of numerous drugs, making it a crucial factor in predicting drug pharmacokinetics. By studying the interaction between UGT1A8 and drug candidates, researchers can optimize drug dosing regimens and predict potential drug-drug interactions.
- Toxicity Assessment and Mitigation:
- UGT1A8’s involvement in the detoxification of drugs and toxins makes it an essential target for toxicity assessment. By evaluating the impact of UGT1A8 on drug metabolism, researchers can identify potential toxicity concerns early in the drug development process and adjust the drug’s structure or dosing regimen accordingly.
- High-Throughput Screening Platforms:
- In Vitro and In Vivo Models:
- Understanding the role of UGT1A8 in drug metabolism can inform the discovery and optimization of new drug candidates. By targeting UGT1A8 or its substrates, researchers can develop novel therapies with improved pharmacokinetic profiles and reduced toxicity.
- Appearance: Lyophilized powder.
- Endotoxin Level: <1.0 EU/μg, determined by LAL method.
- Purity: Greater than 90% as determined by reducing SDS-PAGE.
- Storage & Stability: Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer. It is recommended to freeze aliquots at -20°C or -80°C for extended storage.
