What does glucuronidation do to drugs?
Conjugation. Glucuronidation, the most common phase II reaction, is the only one that occurs in the liver microsomal enzyme system. Glucuronides are secreted in bile and eliminated in urine. Thus, conjugation makes most drugs more soluble and easily excreted by the kidneys.
What is meant by glucuronidation?
n. a metabolic process by which drugs or other substances are combined with glucuronic acid to form more water-soluble compounds, which are more readily excreted by the kidneys or in bile. Glucuronidation is the most prevalent of the Phase II reactions of drug metabolism.
What is the enzyme of glucuronidation?
Glucuronidation reactions are catalyzed by a family of enzymes called uridine diphosphate-glucuronosyltransferases (UGTs), which likely evolved in response to the need to excrete lipophilic compounds from the body.
What is glucuronidation pathway?
Glucuronidation is the major pathway in phase II metabolism and accounts for approximately 35% of drug conjugation. UGTs are microsomal membrane-bound and catalyze the transfer of a glucuronate group of uridine diphosphoglucuronate (UDPGA, a co-substrate) to the functional group of specific substrates.
What is oxidation of a drug?
The main chemical reactions that affect the stability of a drug are oxidation and hydrolysis. Oxidation involves the removal of electrons from a molecule (or the addition of oxygen) and such reactions can be initiated by light, heat or certain trace metals.
What is oxidation in drug metabolism?
Phase I modifications alter the chemical structure of the drug, usually by oxidation. Oxidation typically results in metabolites that still retain some of their pharmacological activity. For example, the common anxiolytic drug diazepam is transformed into desmethyldiazepam and then to oxazepam by phase I modification.
How do you support 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 are the 3 phases of drug action?
Drug action usually occurs in three phases: Pharmaceutical phase. Pharmacokinetic phase. Pharmacodynamic phase.
Where are most drugs oxidized?
They are present in the smooth endoplasmic reticulum of cells (Fig. 2.9), particularly in the liver, which is the major site of drug oxidation; the amounts in other tissues are low in comparison.
How are drugs oxidised in the body?
Metabolic Enzymes The most common and important enzyme group involved in the Phase I metabolism of drugs is the cytochrome P450 (CYP450) superfamily of enzymes. This group of enzymes acts as a catalyst for the oxidation of many drugs. It can, in turn, also be induced or inhibited by many drugs and other substances.
How are glycosidic bonds involved in glucuronidation?
These linkages involve glycosidic bonds. Glucuronidation consists of transfer of the glucuronic acid component of uridine diphosphate glucuronic acid to a substrate by any of several types of UDP-glucuronosyltransferase .
Which is an example of glucuronidation in the liver?
UDP-glucuronic acid (glucuronic acid linked via a glycosidic bond to uridine diphosphate) is an intermediate in the process and is formed in the liver. One example is the N-glucuronidation of an aromatic amine, 4-aminobiphenyl, by UGT1A4 or UGT1A9 from human, rat, or mouse liver. The substances resulting from glucuronidation are…
What are the products of glucuronidation in UDPGA?
Glucuronic acid exists in UDPGA in the 1α-configuration, but the products of conjugation are β-glucuronides ( 8; Figure 24.9 ). This is due to the mechanism of the reaction being a nucleophilic substitution with inversion of configuration (SN 2 ).
What is the role of glucuronidation in critical care?
Glucuronidation is a well-characterized phase II metabolic pathway that has high capacity and provides rapid drug inactivation via the polar glucuronide metabolites produced. Lara Primak, Jeffrey L. Blumer, in Pediatric Critical Care (Third Edition), 2006 Glucuronidation.