Biotransformation of organic xenobiotics normally proceed in a first step of oxidation phase i that introduces a reactive group in the xenobiotic, and a second step of conjugation phase ii with a nontoxic endogenous metabolite that yields an excretable product. Metabolism of xenobiotics metabolism of xenobiotics. Many xenobiotics that enter the body are lipophilic, and the pollutants. Induction of phase ii detoxification enzymes by t 3 represents an additional hepatoprotective mechanism, due to their roles in xenobiotic biotransformation of. Enzymatic biotransformation reactions of xenobiotic substances after absorption involve phase i and phase ii biotransformation reactions, which usually work together in a sequential manner to convert xenobiotics into more readily excretable metabolites yu, 2005. This work is licensed under a creative commons attribution. The mammalian drug biotransformation systems are thought to have first evolved from the need to detoxify and eliminate plant and bacterial bioproducts and toxins, which later extended to drugs and other environmental xenobiotics. Polar xenobiotics are easily eliminated by the body through urine, sweat, etc.
This page provides homology modeled 3d structures of all enzymes figure 1 e. Catabolic reactions include oxidation, reduction, and hydrolysis. Xenobiotics, biotransformation, drug synergism and the. Biotransformation of xenobiotics and factors affecting it. Biotransformation can be defined as the use of biological systems. Induction of phase i, ii and iii drug metabolismtransport. Drug metabolizing enzymes and biotransformation reactions 1 nalia at penner, caoline r woodward and, chandra prakash a. Liver and biotransformation of xenobiotics functions.
Xenobiotics can be stored within a variety of different body organs and tissues. Drugs can be eliminated from the systemic circulation unchanged by renal excretion e. Biotransformation of xenobiotics an overview sciencedirect topics. Xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities. Scientific opinion on the substantiation of health claims. The following points highlight the two main phases of biotransformation of toxicants. However, if you are among those that have been searching for answers to phase 2 metabolism reactions, phase 1 and phase 2 reactions in drug metabolism ppt, lecture notes on xenobiotics, xenobiotic metabolism ppt, xenobiotic metabolism pdf, induction of phase i ii and iii drug metabolism transport by xenobiotics, phase 1 reactions biotransformation, drug. It increases hydrophilicity of xenobiotics by introducing polar functional groups such oh. Biotransformation of xenobiotics and hormones eolss.
Biotransformation is the process by which a xenobiotics is chemically altered by the body. Induction of phase i, ii and iii drug metabolismtransport by xenobiotics. Xenobiotic metabolism and detoxification especially for drugs are separated into three different phases of reaction. Enzymes implicated in phase ii deconjugating reactions including. Biotransformation is a process specifically to make agents more polar and excretable. Biotransformation of xenobiotics biotransformation vs. Enzymatic reactions that add or expose functional groups to xenobiotics such as oh, sh, nh2. A vicious takedown of the phase i phase ii classification system is available from josephy et al 2005. Since the liver is the primary site for biotransformation, it is also potentially vulnerable to the toxic action of a xenobiotic that is activated to a more toxic compound. Evans dvm, ms, phd, dact, dabvt, in small animal toxicology third edition, 20. Biotransformation can detoxify or bioactivate xenobiotics to. The physiology and biochemistry of biotransformation.
Biotransformation changes the properties of a xenobiotic usually from a lipophilic form that favors absorption to a hydrophilic form favoring excretion in the urine or bile. Phase 1 reactions oxidative reactions most important and most common, almost all drugs that undergo phase 1 biotransformation undergo oxidation at some stage or other. Recently its application is seen as an efficient, cost effective, and easily applicable approach for the valorization of agricultural wastes with potentials of enhancing existing bioactive. In addition to the liver, biotransformation processes occur in plasma, in the lungs, in the gastrointestinal tract and in the skin. Phase ii reactions enzymatic reactions that result in the conjugation of large watersoluble, charged polarbiomolecules to xenobiotics for these reactions to occur, a functional group must be present on either the parent compound or its phase i product. Fetzner encyclopedia of life support systems eolss the products of partial biodegradation, or biotransformation, or cometabolic conversion of a xenobiotic may be less harmful as the original compound, or they may be as hazardous or even more hazardous as the original compound. The liver has enzymes that facilitate chemical reactions such as oxidation, reduction, and hydrolysis of xenobiotics phase i. Discovery of a widespread metabolic pathway within and.
Reduced metabolising capacity of phase ii enzymes can lead to toxic effects of clinically used drugs. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. Liver and biotransformation of xenobiotics functions of. Functional medicine universitys functional diagnostic medicine training program module 6. A low capacity exists in the skin, intestines, testes, and placenta. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities.
Phase i metabolizing enzymes, phase ii metabolizing enzymes, pglycoprotein, multidrug resistanceassociated protein, organic anion transporting polypeptide 2, aryl hydro carbon receptor, pregnane x receptor, constitutive androstane receptor, peroxisome prolifera. Start studying chapter 6 biotransformation of xenobiotics. Biotransformation of xenobiotics request pdf researchgate. Biotransformation of xenobiotics can also result in the formation of chemical intermediates.
Conclusion xenobiotics are any substances foreign to the body biotransformation aims to convert water insoluble xenobiotics to water soluble and excrete via urine or bile in phase i reaction chemical alternations dramatically changes. The pointless attachment to phase i and phase ii classification structure. Chapter 6 biotransformation of xenobiotics flashcards. This page provides homology modeled 3d structures of all enzymes figure 1e. Induction of phase i, ii and iii drug metabolismtransport by. Xenobiotics are unwanted chemicals in the environment and the diet that the body is exposed to. The liver is the principal, but not the only, site of xenobiotics biotransformation. In the first phase the oxidation by cytochrome p450 introduces a hydroxyl group and. To defense the body against xenobiotic substances, an array of biotransformation reactions or metabolic reactions is undergone. Choose from 26 different sets of biotransformation xenobiotic flashcards on quizlet. However, lipophilic xenobiotics require a sophisticated. Phase i reactions involve hydrolysis, reduction, and oxidation. Liver composes of four lobes divided into lobules which are surrounded by blood vessels.
Phase ii reactions enzymatic reactions that result in the conjugation of large watersoluble, charged polarbiomolecules to xenobiotics for these reactions to occur, a functional group must be present. The biochemical transformation of xenobiotics, such as alcohol, nicotine and drugs is a prime activity of the liver. This occurs by introduction of a polar group, such as hydroxyl oh, amine nh 2, and sulfhydryl sh groups for example, phenylbutazone is a benzene compound. Biotransformation of xenobiotics can dominate toxicokinetics and the metabolites may reach higher concentrations in organisms than their parent compounds. Bioactivation changes that enhance excretion chemically distinct metabolite hydrophilicity membrane permeability reabsorption effects on biological half life t 12 biotransforming enzymes specificities. Ii biotransformation of xenobiotics and hormones osmo hanninen encyclopedia of life support systems eolss the oxidation is a very common step in the metabolism of xenobiotics. Unesco eolss sample chapters physiology and maintenance vol. Xenobioticmetabolizing enzymes can be divided into phase i, phase ii, and transporter enzymes. Pdf biotransformation phase i hydrolysis gerardo isaac. Ii biotransformation of xenobiotics and hormones osmo hanninen encyclopedia of life support systems eolss spring, which was translated into many languages draw the attention of great public on the environmental problems caused by the chemicals spread for various purposes in nature. The two phases in the biotransformation of lipophilic naphthalene. The liver has enzymes that facilitate chemical reactions such as oxidation, reduction, and.
Toxicants that are lipophilic, nonpolar, and of low molecular weight are readily absorbed through the cell membranes of the skin, gi tract, and lung. Nacetylation of xenobiotics is performed by nacetyltransferases nat nacetylation is a major route of biotransformation for xenobiotics containing an aromatic amine rnh2. Formally, biotransformation of xenobiotics as well as endogenous compounds is subdivided into phase i and phase ii reactions. The biotransformation of great variety of xenobiotic compounds involves oxidation process. Biotransformation of organic xenobiotics normally proceed in a first step of oxidation phase i that introduces a reactive group in the xenobiotic, and a second step of. Lipophilic xenobiotics are often first metabolized by phase i enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Activate naturalendogenous compounds for normal function. Phase i reactions, also known as functionalization reactions, involve the transformation of lipophilic drugs into a more watersoluble compound. Phase ii drug metabolizing enzymes play an important role in biotransformation of endogenous compounds and xenobiotics to more easily excretable forms as well as in the metabolic inactivation of pharmacologically active compounds.
More generally, xenobiotic metabolism from the greek xenos stranger and biotic related to living beings is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organisms normal. Biotransformation also serves as an important defense mechanism since toxic xenobiotics and body wastes are converted into less harmful substances and substances that can be excreted from the body. Basic concepts 4 interaction with these enzymes may change the toxicant to either a less or a more toxic form. Phase i of biotransformation is mediated by inducible cytochrome p450 dependent monooxygenases cyp. To find drugs that are metabolized by specific phase i, phase ii or transporter enzymes, users can perform a search by clicking on biotransformation. Metabolic biotransformation of xenobiotics mammalian. Phase 2 biotransformation reaction animated biology with arpan. Biotransformation includes chemical modification of the xenobiotic by oxidation. Biotransformation reactions grouped as phase i functional group modification and phase ii conjugation. Metabolism of xenobiotics metabolism of xenobiotics occurs in two phases phase 1, the major reaction involved is hydroxylation. For other authors, the drug metabolism comprises only the biotransformation step and consequent chemical modifications of drugs by the enzymes. The metabolic biotransformation reactions of xenobiotics encompasses changes in these chemicals produced by biological environments. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds.
Depending on the anatomic and physiologic relationships between the storage depot and the target organs and tissues for a specific toxicant, storage of toxic xenobiotics can. Biotransformation, in fact, is the inactivation of pharmacological action of drugs. Biotransformation is one of the most important determinants of xenobiotic toxicity in organisms and is becoming increasingly important in environmental toxicology and risk assessment 1, 2. Phase i involves catabolic reactions that break down the toxicant into various components. Liver is the second largest organ in the body the largest is skin, weighing approximately 1,5 kg. Transferases cytosolic or bound in membranes of er catalyze. Phase i reactions introduce polar groups into the chemical, including carboxyl, epoxide, hydroxyl, sulfhydryl, amine, hydroxylamine, and imine. Biodegradation of xenobiotics encyclopedia of life. In addition to hydroxylation, a wide range of reactions also take place including deamination, dehalogenation, desulfuration, epoxidation, peroxygenation, and reduction 6. Phase i reactions o oxidation most xenos o reduction azonitro compounds o hydrolysis. Nov 23, 2012 metabolism of xenobiotics metabolism of xenobiotics occurs in two phases phase 1, the major reaction involved is hydroxylation. Catabolic reactions include oxidation, reduction, and. Exogenous compounds xenobiotics must be metabolized before they can be excreted.
This chapter focuses on phase ii biotransformation reactions also called. Due to the biotransformation, the molecular structure of a. Phase i and phase ii biotransformation reactions deranged. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Biotransformation of xenobiotics pharmacology 23,331 views enzymatic modification of the drug occurring within the living organisms or chemical transformation a drug goes through in living organisms or biological fluids is known as biotransformation. Aug 06, 2017 conclusion xenobiotics are any substances foreign to the body biotransformation aims to convert water insoluble xenobiotics to water soluble and excrete via urine or bile in phase i reaction chemical alternations dramatically changes the biological property cyt. Phase i reactions involve hydrolysis, reduction, and. To make use of a compound or to facilitate its excretion increases the water solubility of a compound divided in two phases, phase i and phase ii. Biotechnology vol x biodegradation of xenobiotics s. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
Unlike other phase ii reactions, acetylation masks an amine with a nonionizable group and are less water soluble than the parent compound. Reactions of biotransformation phase ii the reactions render xenobiotics even more watersoluble enabling excretion of them into the urine or bile, convert the biologically active products of phase i reactions into less active or inactive species. Some authors consider the biotransformation as one of the steps of drug metabolism, which includes absorption, distribution, biotransformation, and excretion 26. Learn biotransformation xenobiotic with free interactive flashcards. If biotransformation does not occur, drugs may have longer duration of action, and undesired effects are observed along with desired ones. Biotransformation an overview sciencedirect topics. The main evolutionary goal of biotransformation is to increase the rate of excretion of xenobiotics or drugs. The biotransformed metabolite is more toxic than the original compound. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Drug metabolizing enzymes and biotransformation reactions 1 nalia at penner, caoline r woodward and, chandra prakash. Biotransformation is the process by which substances that enter the body are changed from hydrophobic to hydrophilic molecules to facilitate elimination from the body.
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