Liver is the second largest organ in the body the largest is skin, weighing approximately 1,5 kg. The metabolic biotransformation reactions of xenobiotics encompasses changes in these chemicals produced by biological environments. Biotransformation reactions grouped as phase i functional group modification and phase ii conjugation. This page provides homology modeled 3d structures of all enzymes figure 1e. Xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities. To make use of a compound or to facilitate its excretion. Overview major phase i and phase ii enzymes reaction mechanisms, substrates. 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. Introduction of phase i, phase ii drug metabolizing enzymes and phase iii drug transporters drug metabolizing enzymes dmes play central roles in the metabolism, elimination.
In addition to hydroxylation, a wide range of reactions also. 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. Humans are exposed daily to a wide variety of foreign compounds called xenobioticssubstances absorbed across. A low capacity exists in the skin, intestines, testes, and placenta. Nov 23, 2012 metabolism of xenobiotics metabolism of xenobiotics occurs in two phases phase 1, the major reaction involved is hydroxylation. Activate naturalendogenous compounds for normal function. These modified compounds are then conjugated to polar compounds in phase ii reactions. 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. Biotransformation includes chemical modification of the xenobiotic by oxidation. The role of biotransformation in the estrogenicity of xenobiotics. Chapter 6 biotransformation of xenobiotics flashcards quizlet. The pointless attachment to phase i and phase ii classification structure.
Unlike other phase ii reactions, acetylation masks an amine with a nonionizable group and are less water soluble than the parent compound. This page provides homology modeled 3d structures of all enzymes figure 1 e. Polar xenobiotics are easily eliminated by the body through urine, sweat, etc. The biotransformation of benzene requires both phase i and phase ii reactions. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2, sh or cooh to slightly increase hydrophilicity. Conjugation, role, fate of products, description and examples. Biotransformation can detoxify or bioactivate xenobiotics to. Examples of each type of conjugation have been illustrated below. Biotransformation an overview sciencedirect topics. The liver is the principal, but not the only, site of xenobiotics biotransformation. Ii biotransformation of xenobiotics and hormones osmo hanninen encyclopedia of life support systems eolss spring, which was translated into many.
Metabolism of xenobiotics metabolism of xenobiotics occurs in two phases phase 1, the major reaction involved is hydroxylation. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Biotransformation of xenobiotics and hormones eolss. In addition to hydroxylation, a wide range of reactions also take place including deamination, dehalogenation, desulfuration, epoxidation, peroxygenation, and reduction 6. 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. Edward croom, in progress in molecular biology and translational science, 2012. In general, these conjugates are more soluble in water and more readily excretable. Involves the complexing or conjugation of xenobiotics with relatively large and. However, lipophilic xenobiotics require a sophisticated. Or, one may instead make use of parkinson and ogilvies biotransformation of xenobiotics, a chapter probably from casarett and doulls toxicology.
Phase ii reactions involve several types of endogenous metabolites that may form conjugates with the xenobiotics or their metabolites. Biotransformation is the chemical modification or modifications made by an organism on a chemical compound. 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. This work is licensed under a creative commons attribution. 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. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. The biotransformed metabolite is more toxic than the original compound.
Oglucuronidation of phenolic drugs or other xenobiotics is often in. What are the differences between these two phases of drug biotransformationmetabolism. Formally, biotransformation of xenobiotics as well as endogenous compounds is subdivided into phase i and phase ii reactions. Many phase i metabolites are not sufficiently polar to be directly excreted by the kidneys. Nacetylation of xenobiotics is performed by nacetyltransferases nat nacetylation is a major route of biotransformation for xenobiotics containing an aromatic amine rnh2. Due to the biotransformation, the molecular structure of a drug is commonly changed to be more hydrophilic and the substances can be readily eliminated from the body 2.
Mar 31, 2020 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 metabolism liver, xenobiotics. 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. Induction of phase i, ii and iii drug metabolismtransport. The two phases in the biotransformation of lipophilic naphthalene. Basic concepts 5 phase ii reactions involves the binding of molecules to either the original toxic molecule or the toxic molecule metabolite derived from the phase i reactions. Biotransformation of xenobiotics pharmacology 23,286 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.
Start studying chapter 6 biotransformation of xenobiotics. Liver and biotransformation of xenobiotics functions. To make use of a compound or to facilitate its excretion increases the. Biotransformation of organic xenobiotics normally proceed in a first step of oxidation phase i that introduces a reactive group in the xenobiotic, and a. More generally, xenobiotic metabolism from the greek xenos stranger and biotic. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds. Phase i of biotransformation is mediated by inducible cytochrome p450 dependent. Conjugative phase ii dmes include uridine 5 diphospho udp glucuronosyltransferase s ugt s, sulfotransferase s sults, glutathione s transferase s gsts, n acetyltransferase s nats, and methyl. Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal. Overview major phase i and phase ii enzymes reaction mechanisms, substrates enzyme inhibitors and inducers genetic polymorphism detoxification metabolic activation fda guidances related to biotransformation. As illustrated in figure 5, benzene is biotransformed initially to phenol by a phase i reaction oxidation. Lipophilic xenobiotics are often first metabolized by phase i enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Phase i reactions n, o, sdealkylation n, s, poxidation oxidative deamination phase ii reactions conjugation reactions the addition of polar groups carbohydrate derivatives, amino acids.
These reactions expose or introduce a functional group oh, nh 2, sh, or cooh, and usually result in only a small increase in hydrophilicity. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. On top of that, biotransformation can occur when drugs undergo further metabolic steps following conjugation, including things like covalent binding to dna and proteins. The overall purpose of the two phases of metabolism of xenobiotics is to increase their water solubility. Functional medicine universitys functional diagnostic medicine training program module 6.
Introduction of phase i, phase ii drug metabolizing enzymes and phase iii drug transporters drug metabolizing enzymes dmes play central roles in the metabolism, elimination andor detoxification of xenobiotics or exogenous compounds introduced into the body meyer, 1996. This chapter addresses the phase ii biotransformation reactions that a drug or. Phase ii reactions enzymatic reactions that result in the conjugation of large watersoluble, charged polarbiomolecules to xenobiotics for these reactions to occur, a. Biotransformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and. This chapter focuses on phase ii biotransformation reactions also called. First biotransformation phase biotransformation itself in the first phase new functional groups are inserted to the molecule of xenobiotic. In contrast with phase i enzymes biotransformation, phase ii conjugating enzymes have received less attention. The liver has enzymes that facilitate chemical reactions such as oxidation, reduction, and hydrolysis of xenobiotics phase i. Phenol has a structure including a functional hydroxyl group that is then conjugated by a phase ii reaction sulfation to phenyl sulfate.
Phase i and phase ii biotransformation reactions deranged. In phase i, enzymes such as cytochrome p450 oxidases introduce reactive or polar groups into xenobiotics. Phase ii reactions include glucuronidation, sulfation, acetylation. The main evolutionary goal of biotransformation is to increase the rate of excretion of xenobiotics or drugs. Xenobiotics are unwanted chemicals in the environment and the diet that the body is exposed to. Choose from 26 different sets of biotransformation xenobiotic flashcards on quizlet.
Phase i and phase ii biotransformation reactions catalyzed by xenobiotic biotransforming enzymes are generally divided into two groups. Mar 16, 2014 what are the differences between these two phases of drug biotransformation metabolism. Possible utilization of some phase ii enzymes biotransformation for xenobiotic. Metabolic biotransformation of xenobiotics mammalian. Xenobioticmetabolizing enzymes can be divided into phase i, phase ii, and transporter enzymes. These compounds are then subjected to phase ii reactions, also known as. Phase i reactions introduce polar groups into the chemical, including carboxyl, epoxide, hydroxyl, sulfhydryl, amine, hydroxylamine, and imine. 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. 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. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds xenobiotic biotransformation is accomplished by a limited number of enzymes.
A vicious takedown of the phase i phase ii classification system is available from josephy et al 2005. Biotransformation of xenobiotics linkedin slideshare. Xenobiotics, biotransformation, drug synergism and the. Transferases cytosolic or bound in membranes of er catalyze. Chapter 6 biotransformation of xenobiotics flashcards. May 18, 2016 phase 2 biotransformation reaction animated biology with arpan. Biotransformation of xenobiotics pharmacology 23,286 views enzymatic modification of the drug occurring within the living organisms or chemical transformation a drug goes through in living. Although phase i drug metabolism occurs in most tissues. Phase i reactions involve hydrolysis, reduction, and oxidation. Induction of phase i, ii and iii drug metabolismtransport by. Biotransformation is the process by which a xenobiotics is chemically altered by the body. 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. In the first phase the oxidation by cytochrome p450 introduces a hydroxyl group and in the. Metabolism of xenobiotics metabolism of xenobiotics.
The physiology and biochemistry of biotransformation. In general, biotransformation reactions are divided into two broad. To find drugs that are metabolized by specific phase i, phase ii or transporter enzymes, users can perform a search by clicking on biotransformation. Phase i metabolites if not readily excretable or contain component ends, combine with endogenous substrates like glucuronic acid, sulphuric acid, amino acid or acetic acid, to undergo conjugation reactions, yielding more excretable drug conjugates which are excreted by the kidneys. Currently, data from in vivo preclinical and in vitro human tissue studies are used in predicting the safety and human pharmacokinetics, and assessing the potential of a new chemical entity nce as a successful. Phase ii biotransformation reactions include glucuronidation, sulfonation more commonly called sulfation, acetylation, methylation, and conjugation with. The final product is usually water soluble and, therefore, easier to excrete from the body. Phase 2 biotransformation reaction animated biology with arpan.
Learn vocabulary, terms, and more with flashcards, games, and other study tools. Drug metabolizing enzymes and biotransformation reactions 1 nalia at penner, caoline r woodward and, chandra prakash a. 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. These reactions are catalysed by transferase enzymes such as glutathione stransferases. Reduced metabolising capacity of phase ii enzymes can lead to toxic effects of clinically used drugs.
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