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Genomics and Drug-Metabolizing Enzymes and Its Application in Drug Delivery: Evaluating the Influence of the Microbiome

Chapter

Abstract

Biotransformation or metabolism is responsible for elimination of 70% of drugs available in the market today [1]. Drug-metabolizing enzymes (DMEs) are an assorted group of enzymes responsible for metabolizing xenobiotics such as drugs, carcinogens, pesticides, and food toxicants as well as endogenous compounds such as prostaglandins, steroids, and bile acids [2, 3]. R.T. Williams coined the concept of two-phase elimination of xenobiotics; reactions such as oxidation, reduction, and hydrolysis are categorized as phase I or activating reactions, while conjugation reactions constitutes phase II reactions and are generally detoxifying in nature [4]. Cytochrome P450 (CYP) families of enzymes are responsible for catalyzing majority of phase I reactions. Phase I reactions convert lipophilic molecules to their water-soluble counterparts [4]. Phase II reactions are catalyzed by enzymes such as uridine diphosphate glucuronosyltransferase (UGT), glutathione transferases (GSTs), N-acetyltransferase (NAT), and sulfotransferases (SULTs) [4]. Phase II enzymes catalyze conjugation of water-soluble molecules to intermediates of phase I reactions for the purpose of improving water solubility. In most cases, the net outcome of both phase I and phase II types of reactions is to impart hydrophilicity to xenobiotics and facilitate their elimination from the body. However, phase I and phase II reactions can also activate inert compounds to pharmacologically active entities [5], toxic end products, and procarcinogens into carcinogenic compounds [4, 6, 7]. CYPs and phase II metabolizing enzymes are known to exhibit polymorphism and have been associated with interindividual variability in drug response and toxicity.

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.USF Health-College of PharmacyTampaUSA

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