Phase i and phase ii biotransformation reactions catalyzed by xenobiotic biotransforming enzymes are generally divided into two groups. The use of enzymes for technical applications has become increasingly important in different areas of biotechnology such as the food or pharmaceutical industries. 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. Within the body is a magnificent assembly of chemical reactions, which is well orchestrated and called upon as needed. Biotransformation an overview sciencedirect topics. Biotransformation is the enzymecatalyzed conversion of one chemical into another that may be more or less toxic lech and vodicnik, 1985. Unhealthy function toxins leave the liver unchanged and are stored in. Phase i reactions represent the introduction of functional groups, whereas phase ii reactions are conjugations of such functional groups with endogenous, polar products. The role of biotransformation and bioactivation in.
In general, biotransformation reactions are divided into two broad. Our new crystalgraphics chart and diagram slides for powerpoint is a collection of over impressively designed datadriven chart and editable diagram s guaranteed to impress any audience. Metabolism of drugs is a form of biotransformation which happens to drugs in a body, whereas biotransformation is a more general term which applies equally well to the actions of a. As illustrated in figure 5, benzene is biotransformed initially to phenol by a phase i reaction oxidation. Drug biotransformation an overview sciencedirect topics. These reactions may occur simultaneously or sequentially. Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2. Biotransformation is an essential process for life driven by chemical reactions inside the human body, which involves the conversion of one type of substance into a different one. Biotransformation metabolism of drugs linkedin slideshare. Unhealthy function some stored toxins recirculate in the blood and may contribute to longterm health issues. Biotransformation, in fact, is the inactivation of pharmacological action of drugs.
Polar xenobiotics are easily eliminated by the body through urine, sweat, etc. Feb 17, 20 biotransformation metabolism of drugs 1. Elimination the toxicity of xenobiotic depends on its elimination rate from an organism. Biochemistry, biotransformation statpearls ncbi bookshelf.
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. If biotransformation does not occur, drugs may have longer duration of action, and undesired effects are observed along with desired ones. As the driving force of metabolism, it enables nutrients to be converted into substances that are healthy for the body, pharmaceutical drugs to be converted into active components that treat certain conditions, and. Drug metabolizing organs liver is the heart of metabolism because of its relative richness of enzymes in large amount. Biotransformation is the metabolic process by which the liver alters or modifies substances entering the body, such as drugs. Biotransformation is defined as any chemical alteration of a chemical that occurs because of the intreraction of that chemical with a biological system. Pathways of biotransformation phase i reactions springerlink. Biotransformation is a major mechanism for drug elimination. Ppt biotransformation powerpoint presentation free to.
The presence of any of these functional groups except which of the following will allow a drug to enter phase ii biotransformation without first passing through phase i. Basic concepts 4 interaction with these enzymes may change the toxicant to either a less or a more toxic form. Functional medicine universitys functional diagnostic medicine training program module 6. The process of drug biotransformation is classified into phase i and phase ii reactions, which occur sequentially and in most situations serve to terminate biological activity and enhance elimination. Phase i and phase ii biotransformation reactions deranged. Polar functional groups are either introduced into the molecule or. 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. In the liver, biotransformation involves hydrolysis, oxidation, reduction, or demethylation and conjugation of the metabolite with glycine, glucuronide, sulfate, or hippurate with subsequent secretion into the bile. The role of biotransformation in the estrogenicity of xenobiotics. Various processes have been developed using soluble or immobilized enzymes mainly in aqueous reaction phases. Biotransformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and.
Describe a drug whose biotransformation involves phase 2 reactions preceding phase 1 reactions the hydrazide moiety of isoniazid directly forms an nacetyl conjugate in a phase 2 reaction. Due to the biotransformation, the molecular structure of a. Unhealthy function in the unhealthy liver, intermediate substances are not completely transformed by phase ii enzymes. Biotransformation rates using sorbent phase dosing were 2fold greater than those measured using solventdelivery dosing. 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 biochemistry, such as any drug.
Pdf the role of biotransformation in drug discovery and. First biotransformation phase biotransformation itself in the first phase new functional groups are inserted to the molecule of xenobiotic. Catabolic reactions include oxidation, reduction, and hydrolysis. Biotransformation reactions grouped as phase i functional group modification and phase ii conjugation. Phase i reactions involve hydrolysis, reduction, and oxidation. 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 biotransformations include oxidation, reduction, and hydrolysis reactions. 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. It is convenient to divide drug metabolism into two phases i and ii which sometimes. The liver is the primary biotransforming organ due to its large size and high concentration of biotransforming enzymes.
Activate naturalendogenous compounds for normal function. The phases of metabolic detoxification are performed by three sets of enzymes or proteins, called the phase i. The pathways of biotransformation are divided into phase i, phase ii, and phase iii. Abnormal metabolism of fats lipids leading to abnormalities in the level of fats in the blood stream e. Hydrophilic molecules are less able to cross cellular membranes, hence fluid filterable kidneys. Phenol has a structure including a functional hydroxyl group that is then conjugated by a phase. There is a common misconception that enzymes are unstable and expensive, work only under high dilution, and do not lend themselves well to scalable chemical processing. Biotransformation also plays an essential role in the toxicity of many chemicals due to the metabolic formation of toxic metabolites. Biotransformation sites biotransforming enzymes are widely distributed throughout the body. Chapters 2 and 3 deal with the chemistry of drug biotransformation, describing both phase i asynthetic and phase ii synthetic biotransformations and the enzymes that mediate them.
Phase i of biotransformation is mediated by inducible cytochrome p450 dependent monooxygenases cyp. Biotransformation may convert drugs to active metabolites or inactive sometimes toxic metabolized products. The biotransformed metabolite is more toxic than the original compound. They are a normal aspect of life, participating in the. Chart and diagram slides for powerpoint beautifully designed chart and diagram s for powerpoint with visually stunning graphics and animation effects. Xenobiotic biotransformation takes place predominantly in smooth endoplasmic reticulum, but also in mitochondria, lysosomes and cytosol. Production of metabolites that are more polar than the parent drug usually terminates the pharmacologic action of the parent drug after phase i reactions, similar or different. 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. 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. Reduced metabolising capacity of phase ii enzymes can lead to toxic effects of clinically used drugs. Phase i involves catabolic reactions that break down the toxicant into various components. Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed by several enzymes including cytochrome p450.
Biotransformation is a process in which microorganisms convert organic compounds in to its structurally related products i. However, lipophilic xenobiotics require a sophisticated. Xenobiotic metabolism typically occurs in two phases. Phase 2 biotransformation reaction animated biology with arpan. Biotransformation drug metabolism or biotransformation refers to the biochemical enzymatic conversion of a drug to another chemical form. The biotransformation of benzene requires both phase i and phase ii reactions.
Pharmdrug biotransformation part 1 flashcards quizlet. Biotransformation reactions affecting drugs as well as other xenobiotics are. Humans are exposed daily to a wide variety of foreign compounds called xenobioticssubstances absorbed across the lungs or skin or, more commonly, ingested either unintentionally as compounds present in food and drink or deliberately as drugs for therapeutic or recreational purposes. Chapters 2 and 3 deal with the chemistry of drug biotransformation. Biotransformation is a process by which organic compounds are transformed from one form to another to reduce the persistence and toxicity of the chemical compounds. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound.
Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Biotransformation is a process specifically to make agents more polar and excretable. Phase i reactions convert the parent drug into more polar metabolites through introduction or exposing oh, sh, or nh2 functional groups. Such processes are often categorized into phase i and phase ii reactions. Liver and biotransformation of xenobiotics functions of. Pdf on feb 1, 2005, p david josephy and others published phase i. A free powerpoint ppt presentation displayed as a flash slide show on id. Often these reactions involve the introduction of polar functional groups such as oh to drug molecules to make them more hydrophilic. Mercury is a wellknown example of an inorganic chemical that undergoes biotransformation by bacteria to methylmercury rai et al. Biotransformation occurs through biochemical processes in which hydrophobic compounds of both endogenous and exogenous nature undergo steps towards becoming more hydrophilic, thus promotingfacilitating their metabolism. Chemical biotransformation has been subdivided into two major phases. Biotransformation process that changes substances from hydrophobic to hydrophilic to aid in elimination grease to salt. Biotransformation can be defined as the use of biological systems.
Liver and biotransformation of xenobiotics functions. Biotransformations encyclopedia of life support systems. In the first chapter, the principles underlying drug absorption, distribution, metabolism and elimination are described, with drug metabolism highlighted within the context of these fundamental processes. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing s9 and protein concentrations, causing measured biotransformation rates to be independent of s9 or protein concentrations. Used enzymes perform at the same time metabolism of endogenous compounds. Biotransformations can also be used to synthesize compounds or materials, if synthetic approaches are challenging. Major elimination routes are feces biliary and urine. I was surprised to find a study titled, biotransformation of hop aroma terpenoids by ale and lager yeasts dated all the way back to 2003, considering this is still not something you hear very often. Importance drug metabolism factor in multidrug resistance cancer chemo therapy environmental science bioremediation or persistence in environment 50. Catabolic reactions include oxidation, reduction, and. Many tissues in the body are capable of metabolizing drug,but most drugs are mainly metabolized in the liver by enzymes localized in hepatic microsomes. Biotransformations are chemical reactions that are catalyzed by microorganisms in terms of growing or resting cells or that are catalyzed by isolated enzymes.
Chemical reactions are continually taking place in the body. Penicillin changes to penicilloic acid in presence of enzyme penicilase. In other words, the metabolites are pharmacologically inactive. Phases of metabolism drug biotransformation could be classified into two phases 1. Phase ii biotransform of drugs linkedin slideshare. A low capacity exists in the skin, intestines, testes, and placenta. Phase 1 metabolism involves chemical reactions such as oxidation most common, reduction and hydrolysis. Introduction to phase i and ii metabolisms phase i metabolism. Liver phases 1 and 2 detoxification pathways what are the symptoms of a dysfunctional liver. Biotransformation of hop oils biotransformation, which is the transformation of hop oils in the presence of yeast, is a fascinating processes. 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.
Biotransformation pathways drug metabolism reactions have been divided into two classes. Enzymatic reactions that add or expose functional groups to xenobiotics such as oh, sh, nh2. Biotransformation is the chemical modification or modifications made by an organism on a chemical compound. Measuring in vitro biotransformation rates of super. Because of the high stereo or regioselectivity combined with high product purity and high enantiomeric excesses, biotransformations can be technically superior to traditional.
This chapter addresses the phase ii biotransformation reactions that a drug or its metabolite typically undergo. This work is licensed under a creative commons attribution. Drug biotransformation or metabolism principally occurs in the liver, kidney, skin, and gi tract. 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. 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. Exposure to environmental xenobiotics may be inadvertent and accidental orwhen they are present as. This conjugate serves as a substrate in a phase 1 reaction in which the conjugate is hydrolyzed to form isonicotinic acid.
Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more watersoluble compounds. Introduction biotransformation is defined as the conversion from one chemical form to another synonym metabolism detoxification process these chemical changes takes place within our body in presence of some enzymes e. Xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities. The process takes place through an interaction of substrates with the. There are three possible results of phase 1 metabolism. This process is aided by major range of microorganisms and their products such as bacteria, fungi and enzymes.