Which drugs are metabolized by glucuronide conjugation?
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids.
What is the principle behind glucuronide activity?
The conjugation of a compound with glucuronic acid results in the production of a strongly acidic derivative that is more water-soluble at physiologic pH than the parent compound. This reduces its transfer across membranes, facilitates its dissociation from the receptor, and enhances its elimination in urine or bile.
Which enzyme is involved in glucuronidation reaction?
UGT1A1 is the primary enzyme responsible for glucuronidation of bilirubin. Mutations in the gene that codes for this enzyme result in hereditary unconjugated hyperbilirubinemia (Crigler-Najjar and Gilbert syndrome). UGT2B7 is the major enzyme responsible for glucuronidation of steroids.
What enzyme do cats lack?
Cats lack the major phenol UDP-glucuronosyltransferase (UGT) enzymes, including UGT1A6 and UGT1A9, that glucuronidate acetaminophen and propofol.
How can I increase my glucuronidation?
Supporting Glucuronidation:
- Citrus Fruits: limonene from the peels of oranges, lemons, limes, and grapefruit and believed to induce UGT activity.
- Cruciferous vegetables.
- Dandelion, rooibos, honeybush, and rosemary tea.
- Astaxanthin found in algae, yeast, trout, krill, shrimp, and crayfish.
What is the importance of enzyme induction caused by barbiturate drugs?
Chronic use of barbiturates will cause upregulation, or induction, of the microsomal enzymes (CYPs 1A2, 2C9, 2C19, and 3A4), increasing the metabolism of drugs metabolized by these enzymes. This can lead to patients requiring larger dosages of medication to achieve therapeutic effect and/or increased clearance.
Why are acyl glucuronides important phase 2 metabolites?
Acyl glucuronides are important metabolites of compounds with carboxylic acid moieties and have unique properties that distinguish them from other phase 2 metabolites. In particular, in addition to being often unstable, acyl glucuronide metabolites can be chemically reactive leading to covalent binding with macromolecules and toxicity.
What are @glucuronides?
Glucuronides are an important class of metabolites for xenobiotics such as drugs. In many analytical methods these conjugates are hydrolysed back to the aglycone followed by extraction.
What is glucuronide conjugate metabolism?
Glucuronide conjugate process is perhaps the major and most common route for Phase II metabolism to form water-soluble metabolites.
How are glucuronides excreted from the body?
Glucuronide formation produces hydrophilic conjugates capable of being passively or actively excreted (see record Passive Diffusion Across Membranes) (see record Active Transport of Drugs Across Membranes ). Active excretion can occur both into urine and, for higher molecular weight compounds, into bile.