What is a reactive metabolite?
Reactive metabolites are usually electron deficient molecules and are referred to as electrophiles (molecules containing positive centers). If not detoxified properly, these electrophiles can react with electron rich species, i.e. nucleophiles (molecules containing negative centers), through covalent bond formation.
What is metabolite toxicity?
Toxic metabolites may form as intermediates, side products, or end products of metabolism, and there are numerous examples of how microbial cells arrange metabolic processes in space and time to prevent the accumulation of these metabolites or to divert them away from sensitive biological processes [1].
How does biotransformation happen?
Biotransformation refers to the process by which lipophilic (fat-soluble), xenobiotic (foreign), or endobiotic (endogenous) chemicals are converted in the body by enzymatic reactions to products that are more hydrophilic (water-soluble).
How are drugs metabolised in the body?
Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization; whatever the process, the goal is to make the drug easier to excrete. The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver.
What is a GSH adduct?
GSH is the major low-molecular-weight thiol in mammalian cells. It is involved in the formation of endogenous bioactive eicosanoids and is a source of reducing equivalents in a number of biosynthetic reactions. Although some reactive intermediates can form adducts directly, GST-mediated reactions generally predominate.
What is meant by biotransformation?
What drugs have toxic metabolites?
Acetaminophen (Paracetamol) Another example of toxic metabolites comes in the commonly used pain relief and antipyretic medication acetaminophen, also known as paracetamol, which is extensively metabolized in the liver.
What do you mean by metabolites?
(meh-TA-boh-lite) A substance made or used when the body breaks down food, drugs or chemicals, or its own tissue (for example, fat or muscle tissue). This process, called metabolism, makes energy and the materials needed for growth, reproduction, and maintaining health.
What are the four types of biotransformation process?
Drugs can undergo one of four potential biotransformations: Active Drug to Inactive Metabolite, Active Drug to Active Metabolite, Inactive Drug to Active Metabolite, Active Drug to Toxic Metabolite (biotoxification).
What are the two phases of biotransformation?
Phase I: Yields a polar, water-soluble, metabolite that is often still active. Many of the products in this phase can also become substrates for phase II. Phase II: Yields a large polar metabolite by adding endogenous hydrophilic groups to form water-soluble inactive compounds that can be excreted by the body.
What are the four stages of drug metabolization?
Think of pharmacokinetics as a drug’s journey through the body, during which it passes through four different phases: absorption, distribution, metabolism, and excretion (ADME).
What is 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.
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