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.
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.
What are the 2 phases of metabolism?
Metabolism is often divided into two phases of biochemical reaction – phase 1 and phase 2. Some drugs may undergo just phase 1 or just phase 2 metabolism, but more often, the drug will undergo phase 1 and then phase 2 sequentially.
What are the 3 phases of metabolism?
The metabolism of xenobiotics is often divided into three phases:- modification, conjugation, and excretion.
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 the difference between Phase I and Phase II of drug 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.
Does Phase 2 metabolism occur in the liver?
The liver is the primary site for metabolism. Liver contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways: Phase I (functionalization reactions) and Phase II (biosynthetic reactions) metabolism.
What is oxidation in phase 1 metabolism?
Oxidation – (Figure 1) Oxidation reactions are some of the most common xenobiotic transformations occurring in plants. These Phase I reactions result in either detoxication or activation of the herbicide. and the atom is reduced to water by an electron donor, such as NADPH (equation 1). …
What is first phase metabolism?
Phase 1 metabolism involves chemical reactions such as oxidation (most common), reduction and hydrolysis. There are three possible results of phase 1 metabolism. The drug becomes completely inactive. … One or more of the metabolites are pharmacologically active, but less so than the original drug.
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.
How does polarity affect metabolism?
Metabolism is the enzymatic conversion of one chemical compound into another. Overall, metabolic processes will convert the drug into a more water-soluble compound by increasing its polarity. … This is an essential step before the drug can be excreted in the body fluids such as urine or bile.
Where does Phase 1 and 2 metabolism occur?
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 affects drug metabolism?
Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly chronic liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism). For many drugs, metabolism occurs in 2 phases.
What do phase 2 enzymes do?
Phase 2 enzymes are major detoxification enzymes and an important part of cellular defense against carcinogens, oxidants, and other toxic chemicals. … Moreover, it has also been reported that catalysis of certain substrates by a phase 2 enzyme may actually result in bioactivation of the compounds.
What happens if a drug is not metabolized?
If your body metabolizes a drug too slowly, it stays active longer, and may be associated with side effects. Because of this, your doctor may characterize you as being one of four metabolizer types, with respect to a specific enzyme. Poor metabolizers have significantly reduced or non-functional enzyme activity.
Is first pass metabolism the same as Phase 1?
Phase 1 reactions are often oxidations or hydrolysis reactions, although reductions also occur. In terms of first-pass metabolism in the liver – hydrolysis of pharmacologically inactive esters (prodrugs) to active drugs are important phase 1 reactions.