Fate of chemicals following exposure III: Metabolism (biotransformation)

Metabolism is the sum of all chemical reactions (synthesis and breakdown of body constituents and of foreign compounds) occurring in organisms at the cellular level to sustain life. The main purpose of metabolism is to convert food to energy to run cellular processes, build macromolecule building blocks, i.e., proteins, lipids, nucleic acids, and carbohydrates and eliminate nitrogenous wastes. Metabolism is catalyzed by enzymes, which are proteins in nature. There are thousands of enzymes in an organism catalyzing a great variety of metabolic pathways (e.g., glycolysis, Krebs cycle), the sum of which is called metabolism, and the molecules that are produced during the process (intermediates or final products) are called metabolites. Metabolism allows organisms to grow, maintain their structures, respond to their environment, and reproduce. Metabolism is usually divided into two categories: catabolism or the breaking down of organic matter by cellular respiration, and anabolism, or the building up of cellular components like proteins and nucleic acids. Usually, catabolism releases energy, and anabolism consume energy. These two processes are linked through cofactors, especially through widely distributed pyridine nucleotides in the form of NAD, NADP, and adenine nucleotides in the form of ATP, ADP, and AMP. A primary catabolic process is cellular respiration where starting molecules such as glucose are oxidized in a stepwise fashion to pyruvate and the released energy is captured in the form of ATP and water and carbon dioxide is released as waste products of oxidation. The ATP is in turn used to drive anabolic processes such as amino acid and lipid biosynthesis. In addition to converting food to energy, biosynthesizing cellular components, and eliminating nitrogenous waste, metabolism also covers the biotransformation of foreign chemicals (xenobiotics) through a series of enzyme-catalyzed processes. Biotransformation alters the physicochemical properties of xenobiotics making them accessible into cells by enhancing their absorption across biological membranes and eliminating them via urine or bile by enhancing their hydrophilicity and/or increasing in molecular weight by conjugation. The enzymes responsible for the xenobiotic biotransformation are often called drug-metabolizing enzymes. In the absence of biotransformation, xenobiotics we are routinely exposed to will accumulate and eventually reach toxic levels. This chapter is part of the absorption, distribution, metabolism, and excretion or ADME series; the four main processes governing chemical (including drug) disposition in biological systems. Therefore, this chapter will summarize some fundamental principles of xenobiotic biotransformation (or metabolism) in mammals and the major enzymes involved in this process.