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Biotransformation is the process whereby a substance is changed from one chemical to another (transformed) by a chemical reaction within the body.  Metabolism or metabolic transformations are terms frequently used for the biotransformation process.  However, metabolism is sometimes not specific for the transformation process but may include other phases of toxicokinetics.

Biotransformation is vital to survival in that it transforms absorbed nutrients (food, oxygen, etc.) into substances required for normal body functions.  For some pharmaceuticals, it is a metabolite that is therapeutic and not the absorbed drug.  For example, phenoxybenzamine (Dibenzyline®), a drug given to relieve hypertension, is biotransformed into a metabolite, which is the active agent.  Biotransformation also serves as an important defense mechanism in that toxic xenobiotics and body wastes are converted into less harmful substances and substances that can be excreted from the body.

If you recall, toxicants that are lipophilic, non-polar, and of low molecular weight are readily absorbed through the cell membranes of the skin, GI tract, and lung.  These same chemical and physical properties control the distribution of a chemical throughout the body and it's penetration into tissue cells.  Lipophilic toxicants are hard for the body to eliminate and can accumulate to hazardous levels.  However, most lipophilic toxicants can be transformed into hydrophilic metabolites that are less likely to pass through membranes of critical cells.  Hydrophilic chemicals are easier for the body to eliminate than lipophilic substances.  Biotransformation is thus a key body defense mechanism.

Fortunately, the human body has a well-developed capacity to biotransform most xenobiotics as well as body wastes.  An example of a body waste that must be eliminated is hemoglobin, the oxygen-carrying iron-protein complex in red blood cells.  Hemoglobin is released during the normal destruction of red blood cells.  Under normal conditions hemoglobin is initially biotransformed to bilirubin, one of a number of hemoglobin metabolites.  Bilirubin is toxic to the brain of newborns and, if present in high concentrations, may cause irreversible brain injury.  Biotransformation of the lipophilic bilirubin molecule in the liver results in the production of water-soluble (hydrophilic) metabolites excreted into bile and eliminated via the feces.

The biotransformation process is not perfect.  When biotransformation results in metabolites of lower toxicity, the process is known as detoxification.  In many cases, however, the metabolites are more toxic than the parent substance.  This is known as bioactivation.  Occasionally, biotransformation can produce an unusually reactive metabolite that may interact with cellular macromolecules (e.g., DNA).  This can lead to a very serious health effect, for example, cancer or birth defects.  An example is the biotransformation of vinyl chloride to vinyl chloride epoxide, which covalently binds to DNA and RNA, a step leading to cancer of the liver.

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