|glutathione conjugation||glutathione S-transferases||liver, kidney|
|glycine conjugation||Two step process: XM-ligase (forms a xenobiotic acyl-CoA) Glycine N-acyltransferase (forms the glycine conjugate)||liver, kidney|
Where does Phase 2 of drug metabolism occur?
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.
Where do most Phase 2 biotransformation take place?
The majority of biotransformation takes place within the liver in cells called hepatocytes. However, several of the enzymes for phase I, phase II, and phase III reactions can also occur in extrahepatic tissues, such as adipose, intestine, kidney, lung, and skin.
What are the 2 phases of drug metabolism?
Drug metabolism reactions comprise of two phases: Phase I (functionalization) reactions such as oxidation, hydrolysis; and Phase II (conjugation) reactions such as glucuronidation, sulphate conjugation.
Where does drug metabolism occur?
Most drugs must pass through the liver, which is the primary site for drug metabolism. Once in the liver, enzymes convert prodrugs to active metabolites or convert active drugs to inactive forms.
What is the difference between Phase 1 and Phase 2 metabolism?
Phase I reactions of drug metabolism involve oxidation, reduction, or hydrolysis of the parent drug, resulting in its conversion to a more polar molecule. Phase II reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine.
Do all drugs undergo Phase 1 and Phase 2 metabolism?
This is called conjugation and the product is called a conjugate. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1 metabolism followed by phase 2 metabolism.
What is Phase II reaction?
Phase II reactions include glucuronidation, sulfation, acetylation, methylation, conjugation with glutathione, and conjugation with amino acids (such as glycine, taurine, and glutamic acid). – It is important to understand that these Phase I and II. reactions may occur simultaneously or sequentially.
Which is the second phase of biotransformation?
Phase II processes involve conjugation reactions that add polar functional groups, such as glucose or sulfate, to the Phase I products, to produce what are often even more polar metabolites. Thus these become even more water soluble and can be readily excreted.
Which enzyme is important in the phase 2 reaction?
Phase II drug metabolising enzymes are mainly transferases. This review covers the major phase II enzymes: UDP-glucuronosyltransferases, sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases (mainly thiopurine S-methyl transferase and catechol O-methyl transferase).
What causes slow drug metabolism?
Underlying health conditions can also influence your drug metabolic rate. Some conditions at greater risk of this are chronic liver disorders, kidney dysfunction, or advanced heart failure.
What are the three phases of metabolism?
The metabolism of xenobiotics is often divided into three phases:- modification, conjugation, and excretion.
What are the 2 major goals of drug metabolism?
The purpose of metabolism in the body is usually to change the chemical structure of the substance, to increase the ease with which it can be excreted from the body. Drugs are metabolized through various reactions including: Oxidation. Reduction.
What is the major site of drug metabolism?
Most drugs must pass through the liver, which is the primary site for drug metabolism. Once in the liver, enzymes convert prodrugs to active metabolites or convert active drugs to inactive forms. The liver’s primary mechanism for metabolizing drugs is via a specific group of cytochrome P-450 enzymes.
Why does first pass metabolism occur?
The first-pass metabolism or the first-pass effect or presystemic metabolism is the phenomenon which occurs whenever the drug is administered orally, enters the liver, and suffers extensive biotransformation to such an extent that the bioavailability is drastically reduced, thus showing subtherapeutic action (Chordiya …
What are the four stages of drug metabolization?
Drugs undergo four stages within the body: absorption, distribution, metabolism, and excretion. After a drug is administered, it is absorbed into the bloodstream.