<P> Conjugates and their metabolites can be excreted from cells in phase III of their metabolism, with the anionic groups acting as affinity tags for a variety of membrane transporters of the multidrug resistance protein (MRP) family . These proteins are members of the family of ATP - binding cassette transporters and can catalyse the ATP - dependent transport of a huge variety of hydrophobic anions, and thus act to remove phase II products to the extracellular medium, where they may be further metabolised or excreted . </P> <P> The detoxification of endogenous reactive metabolites such as peroxides and reactive aldehydes often cannot be achieved by the system described above . This is the result of these species' being derived from normal cellular constituents and usually sharing their polar characteristics . However, since these compounds are few in number, it is possible for enzymatic systems to utilize specific molecular recognition to recognize and remove them . The similarity of these molecules to useful metabolites therefore means that different detoxification enzymes are usually required for the metabolism of each group of endogenous toxins . Examples of these specific detoxification systems are the glyoxalase system, which acts to dispose of the reactive aldehyde methylglyoxal, and the various antioxidant systems that remove reactive oxygen species . </P> <P> Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal organ of drug metabolism, although every biological tissue has some ability to metabolize drugs . Factors responsible for the liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut, and that there are very high concentrations of most drug - metabolizing enzyme systems relative to other organs . If a drug is taken into the GI tract, where it enters hepatic circulation through the portal vein, it becomes well - metabolized and is said to show the first pass effect . </P> <P> Other sites of drug metabolism include epithelial cells of the gastrointestinal tract, lungs, kidneys, and the skin . These sites are usually responsible for localized toxicity reactions . </P>

The biotransformation or metabolism of a drug most often occurs in the