Difference between phase 1 and phase 2 biotransformation pdf

Phase 1 detoxification is carried out by 10 different families of enzymes, which are produced with the aid of 35 different genes. 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. The role of cyp2k1 in the biotransformation of endogenous compounds has been linked to hormones catalysis of the 2hydroxylation of 17. Biotransformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and. Overview definition consequences types phase iii in detail enzyme inductioninhibition first pass. This is called conjugation and the product is called a conjugate. Differences of p25 phase 1 and phase 2 tait radio academy. This work is licensed under a creative commons attribution. Phase 2 ejseries 4cylinder engines phase 1 and phase 2 refer to the engines, transmissions and electronics used in subarus aka, phase i and phase ii. Sometimes metabolites retain biological activity and may be toxic.

Drug biotransformation an overview sciencedirect topics. Phase 2 trials typically involve hundreds of patients. Liver and biotransformation of xenobiotics functions. It is catalysed by the cytochrome p450 group of enzymes and other. Biotransformation of benzene into phenol in phase 1 oxidation, which is then conjugated by a phase 2 reaction sulfation to phenyl sulfate image source. Pharmdrug biotransformation part 1 flashcards quizlet. Although phase i drug metabolism occurs in most tissues. Phase 1 reactions normally add a functional group to the foreign molecule which enables the phase 2 reaction to take place. A question commonly asked is, what is the difference between p25 phase 1 and phase 2. Describe a drug whose biotransformation involves phase 2 reactions preceding phase 1 reactions.

In the first phase new functional groups are inserted to the molecule of xenobiotic. Drugs transformed by phase i reactions usually lose pharmacological activity. There is a duct between the sigmoid colon and the liver called the entero. Introduction to phase i and ii metabolisms phase i. Biotransformation is of primary importance to toxicology because the biological activity of toxicants is enhanced or decreased by this process. Dont fall for it, or you will never understand how a threephase system works. Phase 2 enzymes conjugate transfer endogenous molecules to the functional group trailer not lipophilic usually not reactive water soluble products excretable catalyzed by transferases. Yields a polar, watersoluble, metabolite that is often still active. Each participant was served 1 sample of the biotransformation dry hop beer and 2 samples of the standard dry hop beer then asked to identify the sample that was unique.

For example, phase i metabolism converts acetonitrile to hoch2cn, which rapidly dissociates into. The following excerpt from the book defines this distinction. The hydrazide moiety of isoniazid directly forms an nacetyl conjugate in a phase 2 reaction. Even before any of the phases begin, treatments are thoroughly tested in labs, sometimes on animals, in order to gather valuable information about the toxicity of the investigational treatments. Notes on twophase flow, boiling heat transfer, and. Noriyuki k, toshiyuki s, raku s, shinichi i, takashi i, maya k, toshio o, miho o, kuniyo i. Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed.

The insertion of a hydroxyl group allows a phase 2 conjugation reaction to take. Sequential metabolism of 2,3,7trichlorodibenzopdioxin 2,3,7tricdd by cytochrome p450 and udp. Phase i reactions, also known as functionalization reactions, involve the transformation of lipophilic drugs into a more watersoluble compound. Phase i and ii of biotransformation biotransformation refers to the metabolic conversion of endogenous and xenobiotic chemicals compared to more watersoluble compounds. Functional medicine universitys functional diagnostic medicine training program module 6. Biochemistry, biotransformation statpearls ncbi bookshelf. Phase i biotransformation generally consists in oxidative metabolism by. Phase i of biotransformation is mediated by inducible cytochrome p450 dependent monooxygenases cyp. Smooth er, cytosol with lesser amounts in mitochondria, nuclei and.

Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. Drug biotransformation mechanisms are described as either phase i or phase ii reaction types. Even before any of the phases begin, treatments are thoroughly tested in labs, sometimes on animals, in order to. This chapter answers parts from section biv of the 2017 cicm primary syllabus, which expects the exam candidate to describe the mechanisms of drug clearance and metabolism. What is different about phase 2 reactions is that unlike in phase i where. So simple, so easy to explain and so increasingly wrong. Phase 1 metabolism converts benzene into a variety of metabolites, but the major one is phenol. Phase i and phase ii drugametabolizing enzymes are expressed. Understanding the relationship of chemical biotransformation to adverse biological effects is oftentimes. Introduction to phase i and ii metabolisms phase i metabolism.

Phase i involves catabolic reactions that break down the toxicant. Transitioning lab providers to submit national cpt4 codes on cms1500, ub04 or equivalent electronic claims is phase 1 of an overall chdp code conversion. Age may affect the efficiency of biotransformation. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Biotransformation is the process by which substances that enter the body are changed from hydrophobic to hydrophilic molecules to facilitate elimination from the body. Bioaccumulation kinetics vary greatly among organisms and chemicals. A similar argument can be made when deciding whether to implement p25 phase 1 or phase 2. Biotransformationthermodynamicsbioactivation vs detoxificationphase i vs phase ii.

In phase i reactions, a small polar group containing both positive and negative charges is either exposed on the toxicant or added to the toxicant. Basic concepts 4 interaction with these enzymes may change the toxicant to either a less or a more toxic form. Biotransformation of xenobiotics in human intestinal mucosa. In general, human fetuses and newborns have limited abilities to carry out xenobiotic biotransformations. What key differences exist between two and three phase. For these reactions to occur, a functional group must be present on either the parent compound or its. More generally, xenobiotic metabolism from the greek xenos stranger and biotic.

Although largely localized in the liver they are also found in the small intestine, which is the portal of entry of dietary toxins. Phase 2 metabolism involves reactions that chemically change the drug or phase 1 metabolites into compounds that are soluble. For many drugs, metabolism via cyp450 is the first phase of drug biotransformation, as noted. Specifically, this chapter exists because in question 20 from the first paper of 2016 the official college answer chided the candidates for not knowing enough about phase i and phase ii reactions. Biotransformation an overview sciencedirect topics. Parent drug is altered by introducing or exposing a functional group oh,nh2, sh. Pdf on feb 1, 2005, p david josephy and others published phase i and phase ii drug metabolism. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through. Phase i biotransformation reactions are simple reactions compared to phase ii reactions. 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. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Phase ii reactions involve conjugation of the drug with endogenous charged. Characterization of phase i and phase ii hepatic drug metabolism activities.

Drugmetabolizing enzymes, especially monooxygenases, play a major role in biotransformation and detoxification of many foreign compounds including environmental carcinogens. The distribution of enzymes in the different anatomic compartments of the intra. Why phase ii biotransformation when phase i reactions are not producing sufficiently hydrophilic water soluble or inactive metabolites, the drugs or metabolites formed from phase i. Biotransformation applications fall into two broad categories.

One of the original goals of p25 was spectrum efficiency. These same drugs frequently pass through a phase ii biotransformation reaction. This occurs by introduction of a polar group, such. The main difference between the two phases is system capacity, so the primary reason for. The second phase of clinical trials or studies for an experimental new drug, in which the focus of the drug is on its effectiveness. Phase i and phase ii reactions o phase i characteristics. Types of phase 1 and phase 2 metabolism associated enzymes and cofactors. Rabbit indolethylamine nmethyltransferase threedimensional structure prediction. It is convenient to divide drug metabolism into two phases i and ii. Biotransformation is a metabolic process that takes place mainly in the. Introduction of a polar functional group or modification of an existing functional. Dont fall for it, or you will never understand how. First biotransformation phase biotransformation itself.