Biotransformation

The body is an amazing organism which is able to handle much of what is consumed by it. When foreign chemicals are put in the body, what we think of as drugs, it is able to either eliminate or use them. The term used scientifically for these foreign chemicals, often ones which cannot be produced naturally, are known as xenobiotics. Eventually, all chemicals put into the body end up as waste. The process of getting a chemical from its original structure to waste is known as biotransformation. Biotransformation is defined as the conversion of molecules from one form into another within an organism. When a chemical goes through biotransformation, ultimately one of three things can happen. The chemical can increase its toxicity (known as bioactivation), decrease its toxicity (known as detoxification), or stay the same. The major organ which carries out biotransformation is the liver; however the kidney, lungs, testes, skin, and intestines can play a part in biotransformation processes. In general, the liver hosts enzymatic processes that modify the chemical structure of xenobiotics making them more water-soluble. Increasing the water-solubility of a chemical, or making them more hydrophilic, increases their ability to be eliminated and decreases their half-life.

Enzymes are the catalysts for nearly all biochemical reactions in the body. Without these enzymes, biotransformation reactions would take place slowly or not at all. This can cause major health problems. The enzymes are often known to have a lock and key relationship. This means that the enzyme binding site is a specific shape, and a perfectly matching substrate is needed to bind to and activate the enzyme. If the substrate does not fit into the enzyme, no reaction can occur. An enzyme can have absolute specificity (an enzyme will only catalyze one reaction), group specificity (an enzyme can catalyze any molecule with a specific functional group), and linkage specificity (an enzyme will react with any molecule with a certain chemical bond).

There are two phases of biotransformation; phase I and phase II. During phase I biotransformation, an enzyme exposes or adds a functional group to a xenobiotics. Oxidation and reduction takes place during phase I biotransformation. The most common oxidizing enzyme is cytochrome P450 (cytP450). CytP450 has the ability to reduce xenobiotics under anaerobic (low oxygen) conditions. This causes lipid soluble xenobiotics to become more water soluble. It is during phase I that a substance will become inactive, active, or not change. From this point, many chemical substances can be excreted directly in urine. For those substances that cannot be excreted yet, phase II biotransformation takes place. One of the major phase II pathways in mammals (except cats) is called glucuronidation. During glucuronidation, glucuronic acid is combined with toxins. Glucuronidation almost always results in decreased potency and half life of a chemical. If a xenobiotic makes it to phase II, upon completion it is excreted in urine.

The course of xenobiotics in the body is attempting to be modeled and traced through an organism. This study is known as toxicokinetics. Many factors can influence the biotransformation capacity of the liver including liver pathologies, age, sex, and species differences.

http://web.squ.edu.om/med-Lib/MED_CD/E_CDs/anesthesia/site/content/v02/020160r00.HTM

http://www.eoearth.org/view/article/150674/

http://classes.uleth.ca/200901/biol3440a/BIO3440.3BiotransformationWEB.pdf