Despite these and other shortcomings 91, the traditional classification in phase 1 and 2 reactions remains helpful to structure the wide range of. Phenyl sulphate, the final metabolite is very water soluble and is readily. Difference between phase i and phase ii metabolism. For example, if 500 mg is present in the body at time zero, after metabolism, 250 mg may be present at 1 hour and 125 mg at 2 hours illustrating a half. Phase i metabolism includes oxidation, reduction, hydrolysis, and hydration and isomerization plus rarer misc. The term metabolism is commonly used probably because products of drug transformation are called metabolites.
Hence, drug metabolism is an important aspect of living systems. Metabolism of drugs is usually divided into phase 1 and phase 2. The nats identified to date and involved in human drug metabolism include nat 1 and nat 2. The usual classification of drug metabolism enzymes and reactions as phase i or ii is somewhat misleading, as these reactions affect some drugs in a reverse order phase ii followed by phase i, e. Phase ii biotransform of drugs linkedin slideshare. Some drugs just undergo one or the other but the majority will undergo phase 1 and then phase 2 sequentially. It is convenient to divide drug metabolism into two phases i and ii which sometimes, but. The terms in the table below are a collection of items from the lectures that you should be able to define and relate in a sentence or two to drug metabolism as set out in the notes. Biotransformation is the chemical modification or modifications made by an organism on a chemical compound.
Identification of ugt isoforms was performed using a panel of. They will fill you up and at the same time give you energy and a good dose of vitamins for the day. Despite these and other shortcomings 91, the traditional classification in phase 1 and 2 reactions remains helpful to structure the wide range of reactions and this classification is used below. Heres a day in phase 1, complete with your breakfast, snacks, lunch, and dinner. Fast mimicking of phase 1 and 2 metabolism of acetaminophen using the roxy ec system fast mimicking of phase 1 and 2 metabolism of acetaminophen using the roxy ec system fast mimicking of phase 1 and 2 metabolism of acetaminophen using the roxy ec system figure 1. We elucidated the contribution of udpglucuronosyltransferase ugt isoforms on the glucuronidation of carbinol.
Phase 1 and phase 2 drug metabolism and bile acid production. Vegetables unlimited 2 cups at minimum fast metabolism diet phase 1 smoothies. These enzymes are found in high concentrations in the smooth endoplasmic reticulum of the liver. Hydroxylation of an nmethyl group leads to expulsion of a molecule of formaldehyde, while oxidation of the omethyl groups takes place to a lesser extent.
Abnormal metabolism of fats lipids leading to abnormalities in the level of fats in the blood stream e. Parturition triggers a surge of both phase 1 and phase 2 reactions. Pathways of drug metabolism drug metabolism is divided into. The lack of uniformity of the development of phase 1 oxidative reactions during the early neonatal period reflects the multiplicity of cytochrome p450 hemoproteins, the terminal oxidases responsible for. Modeling of phase 2 metabolism enzymes drug metabolism. Recently, a third phase of metabolism has been proposed phase iii, in recognition of the role of membrane transporters on the biliary excretion of drugs and their metabolites, as well as the ef. The liver is the principal, but not the sole, site of most drug metabolism in the body. The primary objective of drug metabolism is to facilitate a drug s excretion by increasing its water solubility hydrophilicity. The duration and intensity of drug action depend not only on the dose of the drug but also on the rates at which drugs are transformed to products that can be excreted readily by the kidney. Animated video created using animaker phase i and phase ii metabolism in the liver.
Phase ii reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine. Choose from 500 different sets of phase 1 metabolism drug flashcards on quizlet. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Introduction to phase i and ii metabolisms phase i. Phase 2 of the fast metabolism diet is powerful stuff. Little overlap in substrate specificities of the two isoforms appears to exist. This is called conjugation and the product is called a conjugate. During fast metabolism diet phase 1 you can enjoy a number of delicious smoothies. While some drugs may undergo just phase 1 or phase 2, most undergo phase 1 followed by phase 2 in tandem. Whereas phase 1 metabolism involves hydroxylation, oxidation, and reduction pathways, phase 2 metabolism involves primarily conjugation of the phase 1 metabolites with a variety of groups e.
Phase 2 reactions are deficient prenatally in both rodents and primates. We started with an indepth look of phase 1 and how its designed to soothe the adrenal glands into producing a steady and regular stream of feelgood hormones. Fast metabolism diet phase 1, 2 and 3 ultimate guide for. This biotransformation can be deterred by replacing the hydrogen at the paraposition and using fluorine as a bioisostere. Two general categories of drug metabolism occur in the liver. Types of phase 1 and phase 2 metabolism associated enzymes and cofactors learn with flashcards, games, and more for free. Nat 2 is a polymorphic enzyme, a property found to have important pharmacological consequences. Phase i biotransformations include oxidation, reduction, and hydrolysis reactions.
Phase i modification, phase ii conjugation and phase iii further modification and excretion and all three phases actively involve to detoxify and remove xenobiotics from the cells. But phase i metabolism converts acetonitrile to hoch 2 cn, which rapidly dissociates into formaldehyde and hydrogen cyanide, both of which are toxic. Therefore, amcbal culturing makes the heparg cells more suitable for testing metabolism and toxicity of drugs. Often these reactions involve the introduction of polar functional groups such as oh to drug molecules to make them more hydrophilic. Examples of phase i drug substrates are listed in table 4 1. The insertion of a hydroxyl group allows a phase 2 conjugation reaction to take place with the polar sulphate group being added. Oct 23, 20 drug metabolism phase i and phase 2 usmlefasttrack. The involved chemical modifications incidentally decrease or increase a drug s pharmacological activity andor halflife, the most extreme example being the metabolic activation of inactive prodrugs into active drugs, e. Jianda lu, jun xue, in critical care nephrology third edition, 2019. However, benzene can also be oxidized by phase i metabolism to.
Phase 1 reactions phase 1 reactions are classified into oxidation, reduction. Phase 1 and or phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1. Parent drug watersoluble metabolitemore readily excreted from body enzyme drug metabolism involves the enzymatic conversion of. I suggest planning out your meals like this for the week, making your 28 days on the fast metabolism. Phase i and phase ii biotransformation reactions catalyzed by xenobiotic biotransforming enzymes are generally divided into two groups. The metabolism phase is absent for the few drugs that are not transformed. Pathways of drug metabolism drug metabolism is divided into two phases. Cytochrome p450 isozyme system play important role in phase i. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2, sh or cooh to slightly increase hydrophilicity. With respect to metabolism of xenobiotics, it is not just metabolism to electrophilic species or socalled phase i metabolism resulting in toxicity, but also detoxification genes or socalled phase ii metabolism that can be expected to yield important modulating polymorphisms. Glutathione gsh or mercapturic acid conjugations 5. In phase ii more lipophilic groups are conjugated to the. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. In such cases, called firstorder elimination or kinetics, the metabolism rate of the drug is a constant fraction of the drug remaining in the body ie, the drug has a specific halflife.
For instance, a drug containing a benzene group may undergo phase i reactions e. Formally, biotransformation of xenobiotics as well as endogenous compounds is subdivided into phase i and phase ii reactions. Phase ii of metabolism may or may not be preceded by phase i reactions. It is highly variable among drugs and depends on biological conditions. The drug metabolism happening in the liver is termed as hepatic metabolism. Often, phases 1 and 2 pathways work together to help in the removal of the xenobiotic. In this phase, we focus on targeting the adrenals and soothing psychological stress. Phase i reactions convert the parent drug into more polar metabolites through introduction or exposing oh, sh, or nh2 functional groups. Drug metabolism phase i and phase 2 usmlefasttrack. The content has been concisely summarized to help understand various steps involved in the phase 1 and pase 2 metabolism processes of xenobiotics.
These reactions include hydrolysis, reduction, and oxidation. Phase 2 drug metabolism enzymatic conjugation reaction in the intestine and liver to form mostly inactive polar metabolite that is excreted in urine or feces mostly in the cellular cytosol except glucuronidation enzyme, which is a microsomal enzyme. The letrozole phase 1 metabolite carbinol as a novel probe. Phase 2 drug metabolism enzymatic conjugation reaction in the intestine and liver.
In this case, if 500 mg is present in the body at time zero, after metabolism, 450 mg may be present at 1 hour and 400 mg at 2 hours illustrating a maximal clearance of 50 mgh and no specific halflife. Phase 2 metabolism involves reactions that chemically change the drug or phase 1 metabolites into compounds that are soluble enough to be excreted in urine. Drug metabolism is the phase of biochemical transformation of the drug. The enzymecatalyzed reactions of phase i metabolism bind oxygen, hydrogen, water, or amino acids to the lipophilic drug molecule to expose or introduce a hydroxyl oh, amino nh 2, sulfhydryl sh, or carboxyl cooh polar functional group, and thus, result in a modest increase in the parent drugs water solubility. As drug concentration increases, metabolism shifts from firstorder to zeroorder kinetics. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2, sh or cooh to increase reactivity and slightly increase hydrophilicity. Phase i reactions of drug metabolism involve oxidation, reduction, or hydrolysis of the parent drug, resulting in its conversion to a more polar molecule. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. The cytochrome p450 enzyme system is particularly important because many different drugs also can induce or inhibit these enzymes. Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. This chapter focuses on phase ii biotransformation reactions also called. For example, phase i metabolism converts acetonitrile to hoch2cn, which rapidly dissociates. Phase 2 conjugation of a drug can occur in the absence of phase 1 metabolism.
Drug metabolism is the chemical alteration of a drug by the body. Many drugs undergo a number of these reactions main function of phase i metabolism is to prepare the compound for phase ii metabolism mixed function enzyme system found in microsomes of many cells esp liver, kidney, lung. Phase ii reactions involve conjugation of the drug with endogenous charged compounds such glutathionine, glucuronide, and glycine. Phase ii metabolism conjugation of drugs and other xenobiotics with a range of different molecules including glucuronic acid, sulfate, amino acids, acetyl groups, methyl groups and glutathione properties of the enzyme families catalyzing these conjugation reactions. Biotransformation drug metabolism linkedin slideshare. Phase ii reactions include glucuronidation, sulfation, acetylation, methylation. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through. Drug metabolism phase 2 conjugation reactions medicinal chemistry 3rd stage 1. Phase ii enzymes undoubtedly play an important role in the detoxification of various xenobiotics. The hydroxylated product produced from phase 1 reactions can also be conjugated by conjugation enzymes to more hydrophilic products, easier to excrete. The conjugated metabolite has larger size and increased water solubility, which allows for secretion into the bile or urine. Drug metabolism is often considered during drug design. Overview definition consequences types phase iii in detail enzyme inductioninhibition first pass metabolism. Phase i functionalisation reactions phase ii conjugation reactions isomerisation e.
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. Furthermore, they significantly contribute to maintaining of homeostasis by binding, transport or inactivation of biologically active compounds such as hormones, bile acids, or. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and polar compounds so that. Metabolism or biotransformation the conversion from one chemical form of a substance to another. The drug metabolism process occurring in organs other than the figure 1. We really want to flood the body with nutrients that stimulate digestion and the metabolism. Phases of drug metabolism phase 1 drug metabolism functional conversion to polar metabolites in preparation for conjugation mostly in endoplasmic reticulum of the liver oh, nh2, sh, cooh often results in inactive metabolite, although sometimes metabolite more active prepares drug for phase 2 metabolism. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Phase i metabolism definition of phase i metabolism by.
The content is so presented to allow the reader to compare various processes simultaneously and can easily memorize and learn about the topic. Phase i reactions include oxidation especially by the cytochrome p450 group of enzymes, also called mixedfunction oxidases, reduction, deamination, and hydrolysis. Phase i and phase ii reactions of drug authorstream. See more ideas about fast metabolism recipes, food recipes and fast metabolism. Metabolism drug metabolism is the anabolic and catabolic breakdown of drugs by living organisms. Learn phase 1 metabolism drug with free interactive flashcards. Phase 1 drug metabolism functional conversion to polar metabolites in. Concluding, culturing heparg cells in the amcbal yields substantial phase 1 and phase 2 drug metabolism, while maintaining high viability, rendering dmso addition superfluous for the promotion of drug metabolism. Now that your body is blissed out and happy from all those feelgood phase 1 foods, its time to ask it to go to work. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Drugs need to reach the sites of action to elicit their pharmacological effects after administration into the body.
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