Or, one may instead make use of parkinson and ogilvies biotransformation of xenobiotics, a chapter probably from casarett and doulls toxicology. Choose from 26 different sets of biotransformation xenobiotic flashcards on quizlet. Biotransformation can detoxify or bioactivate xenobiotics to. Mar 16, 2014 what are the differences between these two phases of drug biotransformation metabolism. Biotransformation is the process by which a xenobiotics is chemically altered by the body. Biotransformation of organic xenobiotics normally proceed in a first step of oxidation phase i that introduces a reactive group in the xenobiotic, and a. Phase ii reactions include glucuronidation, sulfation, acetylation. Learn vocabulary, terms, and more with flashcards, games, and other study tools. 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 phase i, enzymes such as cytochrome p450 oxidases introduce reactive or polar groups into xenobiotics. May 18, 2016 phase 2 biotransformation reaction animated biology with arpan. Overview major phase i and phase ii enzymes reaction mechanisms, substrates. The liver is the principal, but not the only, site of xenobiotics biotransformation. As illustrated in figure 5, benzene is biotransformed initially to phenol by a phase i reaction oxidation. The biotransformation of benzene requires both phase i and phase ii reactions. Possible utilization of some phase ii enzymes biotransformation for xenobiotic. In general, biotransformation reactions are divided into two broad. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. In contrast with phase i enzymes biotransformation, phase ii conjugating enzymes have received less attention. Phase i of biotransformation is mediated by inducible cytochrome p450 dependent. However, lipophilic xenobiotics require a sophisticated. What are the differences between these two phases of drug biotransformationmetabolism. Phase ii reactions enzymatic reactions that result in the conjugation of large watersoluble, charged polarbiomolecules to xenobiotics for these reactions to occur, a.
Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Examples of each type of conjugation have been illustrated below. The final product is usually water soluble and, therefore, easier to excrete from the body. The role of biotransformation in the estrogenicity of xenobiotics.
The main evolutionary goal of biotransformation is to increase the rate of excretion of xenobiotics or drugs. Involves the complexing or conjugation of xenobiotics with relatively large and. Nov 23, 2012 metabolism of xenobiotics metabolism of xenobiotics occurs in two phases phase 1, the major reaction involved is hydroxylation. In the first phase the oxidation by cytochrome p450 introduces a hydroxyl group and in the. Phase i reactions introduce polar groups into the chemical, including carboxyl, epoxide, hydroxyl, sulfhydryl, amine, hydroxylamine, and imine. Many phase i metabolites are not sufficiently polar to be directly excreted by the kidneys. Formally, biotransformation of xenobiotics as well as endogenous compounds is subdivided into phase i and phase ii reactions. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds xenobiotic biotransformation is accomplished by a limited number of enzymes. Edward croom, in progress in molecular biology and translational science, 2012.
Biotransformation is the chemical modification or modifications made by an organism on a chemical compound. Although phase i drug metabolism occurs in most tissues. The pointless attachment to phase i and phase ii classification structure. Liver and biotransformation of xenobiotics functions. On top of that, biotransformation can occur when drugs undergo further metabolic steps following conjugation, including things like covalent binding to dna and proteins. 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. Biotransformation of xenobiotics and hormones eolss.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. 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. Chapter 6 biotransformation of xenobiotics flashcards. 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. Metabolic biotransformation of xenobiotics mammalian. The biotransformed metabolite is more toxic than the original compound.
The overall purpose of the two phases of metabolism of xenobiotics is to increase their water solubility. Phase 2 biotransformation reaction animated biology with arpan. More generally, xenobiotic metabolism from the greek xenos stranger and biotic. This chapter addresses the phase ii biotransformation reactions that a drug or. To make use of a compound or to facilitate its excretion increases the. Transferases cytosolic or bound in membranes of er catalyze. In general, these conjugates are more soluble in water and more readily excretable. Biotransformation of xenobiotics linkedin slideshare. These compounds are then subjected to phase ii reactions, also known as. This chapter focuses on phase ii biotransformation reactions also called. Functional medicine universitys functional diagnostic medicine training program module 6.
The metabolic biotransformation reactions of xenobiotics encompasses changes in these chemicals produced by biological environments. A vicious takedown of the phase i phase ii classification system is available from josephy et al 2005. Xenobiotics are unwanted chemicals in the environment and the diet that the body is exposed to. This page provides homology modeled 3d structures of all enzymes figure 1 e. Humans are exposed daily to a wide variety of foreign compounds called xenobioticssubstances absorbed across. Metabolism of xenobiotics metabolism of xenobiotics. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2, sh or cooh to slightly increase hydrophilicity. Induction of phase i, ii and iii drug metabolismtransport by. These reactions are catalysed by transferase enzymes such as glutathione stransferases. Activate naturalendogenous compounds for normal function. To find drugs that are metabolized by specific phase i, phase ii or transporter enzymes, users can perform a search by clicking on biotransformation. 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 take place including deamination, dehalogenation, desulfuration, epoxidation, peroxygenation, and reduction 6. Xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities.
A low capacity exists in the skin, intestines, testes, and placenta. These reactions expose or introduce a functional group oh, nh 2, sh, or cooh, and usually result in only a small increase in hydrophilicity. Conjugation, role, fate of products, description and examples. This work is licensed under a creative commons attribution. These modified compounds are then conjugated to polar compounds in phase ii reactions. Xenobiotics, biotransformation, drug synergism and the. Nacetylation of xenobiotics is performed by nacetyltransferases nat nacetylation is a major route of biotransformation for xenobiotics containing an aromatic amine rnh2. 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. Drug metabolizing enzymes and biotransformation reactions 1 nalia at penner, caoline r woodward and, chandra prakash a. 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. 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. Biotransformation includes chemical modification of the xenobiotic by oxidation. Biotransformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and.
The two phases in the biotransformation of lipophilic naphthalene. 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. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds. This page provides homology modeled 3d structures of all enzymes figure 1e. 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 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. Metabolism of xenobiotics metabolism of xenobiotics occurs in two phases phase 1, the major reaction involved is hydroxylation. 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. 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.
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. Oglucuronidation of phenolic drugs or other xenobiotics is often in. 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. 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. Lipophilic xenobiotics are often first metabolized by phase i enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Biotransformation reactions grouped as phase i functional group modification and phase ii conjugation. 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. Reduced metabolising capacity of phase ii enzymes can lead to toxic effects of clinically used drugs. Start studying chapter 6 biotransformation of xenobiotics. Phase ii biotransformation reactions include glucuronidation, sulfonation more commonly called sulfation, acetylation, methylation, and conjugation with. 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. 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.
Chapter 6 biotransformation of xenobiotics flashcards quizlet. Liver is the second largest organ in the body the largest is skin, weighing approximately 1,5 kg. The physiology and biochemistry of biotransformation. Polar xenobiotics are easily eliminated by the body through urine, sweat, etc. First biotransformation phase biotransformation itself in the first phase new functional groups are inserted to the molecule of xenobiotic. 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. Phase i and phase ii biotransformation reactions deranged.
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. Phase i reactions involve hydrolysis, reduction, and oxidation. Phase ii reactions involve several types of endogenous metabolites that may form conjugates with the xenobiotics or their metabolites. Ii biotransformation of xenobiotics and hormones osmo hanninen encyclopedia of life support systems eolss spring, which was translated into many. 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. To make use of a compound or to facilitate its excretion. Unlike other phase ii reactions, acetylation masks an amine with a nonionizable group and are less water soluble than the parent compound. Xenobioticmetabolizing enzymes can be divided into phase i, phase ii, and transporter enzymes.
Phase i and phase ii biotransformation reactions catalyzed by xenobiotic biotransforming enzymes are generally divided into two groups. Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal. 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. In addition to hydroxylation, a wide range of reactions also.
160 321 256 1573 1473 1064 1309 1327 1253 207 451 1314 308 1125 1408 672 1094 871 121 873 1058 320 544 357 436 1292 110 1576 1134 229 1638 352 1169 1542 844 508 1216 811 521 146 1192 272 502 33 1488