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 happens during conjugation in Phase 2 of metabolism?
Phase II reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine. The substances that result from metabolism may be inactive, or they may be similar to or different from the original drug in therapeutic activity or toxicity.
Is conjugation a Phase 2 reaction?
Phase II reactions consist of adding hydrophilic groups to the original molecule, a toxic intermediate or a nontoxic metabolite formed in phase I, that requires further transformation to increase its polarity. These reactions include conjugation reactions, glucuronidation, acetylation, and sulfation.
Is Phase 2 metabolism of drugs by conjugation affected by age?
Usually, age does not greatly affect clearance of drugs that are metabolized by conjugation and glucuronidation (phase II reactions).
Which tri peptide is conjugated to xenobiotics during Phase II metabolism?
To join together, as in a xenobiotic molecule binding with a sugar or glutathione molecule.
Which is phase 2 drug metabolizing reaction?
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.
Why do some drugs inhibit the biotransformation process?
FACTORS AFFECTING BIOTRANSFORMATION
Enzyme inhibition occurs when 2 drugs sharing metabolism via the same isozyme compete for the same enzyme receptor site. The more potent inhibitor will predominate, resulting in decreased metabolism of the competing drug.
Where does Phase 2 metabolism occur?
Phase II metabolism involves the introduction of a hydrophilic endogenous species, such as glucuronic acid or sulfate, to the drug molecule. Enzymes involved in phase II reactions are mainly located in the cytosol, except glucuronidation enzyme, which is also a microsomal enzyme.
What is the purpose of glucuronidation?
Glucuronidation is a major mechanism for the formation of water-soluble substrates from xenobiotics, leading to their elimination from the body in bile or urine.
What is the difference between Phase 1 and Phase 2 metabolism?
The key difference between phase I and phase II metabolism is that the phase I metabolism converts a parent drug to polar active metabolites while phase II metabolism converts a parent drug to polar inactive metabolites. Metabolism (drug metabolism) is the anabolic and catabolic breakdown of drugs by living organisms.
Why does drug metabolism decrease with age?
Ageing is associated with a reduction in first-pass metabolism. This is probably due to a reduction in liver mass and blood flow . As a result, the bioavailability of drugs undergoing extensive first-pass metabolism such as propranolol and labetalol can be significantly increased [53–55].
What are the factors affecting drug metabolism?
Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences. In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults.
How does age factor affect drug metabolism?
Generally, older age is associated with increased blood concentrations of drugs and altered metabolism, reduced effectiveness, and increased risk of adverse reactions for many medications (2).
What is the purpose of glutathione conjugation?
Glutathione conjugation is an important detoxification mechanism. Glutathione (GSH) is a tripeptide found in most of the tissues, especially in high concentrations in the liver, and plays an extremely important role in protecting hepatocytes, erythrocytes, and other cells against toxic injury.
Why are drugs referred to as xenobiotics?
Definition. Xenobiotics are chemicals found but not produced in organisms or the environment. Some naturally occurring chemicals (endobiotics) become xenobiotics when present in the environment at excessive concentrations. The “xeno” in “xenobiotics” comes from the Greek word xenos meaning guest, friend, or foreigner.
Is aspartic acid conjugated?
Some of the first evidence of amino acid conjugation with a herbicide was 2,4-D conjugation to aspartic acid (Figure 29). Other amino acids identified include glutamate, valine, leucine, phenylalanine and tryptophan. The most common amino acids conjugating with xenobiotics in plants are aspartate or glutamate.