by Martin LaBar
Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products. Its rate is an important determinant of the duration and intensity of the pharmacological action of drugs. Drug metabolism can result in toxication or detoxication – the activation or deactivation of the chemical. While both occur, the major metabolites of most drugs are detoxication products.
The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes. Enzymes are crucial to metabolism because they allow organisms to drive desirable but thermodynamically unfavorable reactions by coupling them to favorable ones. Enzymes also allow the regulation of metabolic pathways in response to changes in the cells environment or signals from other cells.
In biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins and other cofactors in order to function properly. Because of the many chemicals that may be involved, pathways can be quite elaborate. In addition, many pathways can exist within a cell. This collection of pathways is called the metabolic network. Pathways are important to the maintenance of homeostasis within an organism.
The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. The Cytochrome P450 monooxygenase system is the most important pathway in this regard. In general, anything that increases the rate of metabolism (e.g., enzyme induction) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action.The opposite is also true (e.g., enzyme inhibition).
The biochemistry of cell metabolism and the endocrine system has been extensively described. Other areas of biochemistry include the genetic code (DNA, RNA), protein synthesis, cell membrane transport, and signal transduction. This article only discusses terrestrial biochemistry (carbon- and water-based), as all the life forms we know are on Earth. Since life forms alive today descended from the same common ancestor, they have similar biochemistries, even for matters that seem to be essentially arbitrary, such as handedness of various biomolecules. It is unknown whether alternative biochemistries are possible or practical.
Various physiological and pathological factors can also affect drug metabolism. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences. 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 livers 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.
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