Biotransformation physiological factors

Xenobiotics are biotransformed by phase I enzymes and phase II conjugation reactions to form a variety of metabolites that are generally more water-soluble and less toxic than the parent compound. Occasionally, the enzymic action of phase I or II systems leads to the formation of unstable intermediates or reactive metabolites that are toxic or carcinogenic. Many physiological factors influence the rate of xenobiotic metabolism and the relative importance of different pathways of metabolic activation or detoxication. 

To describe bio accumulation, physiological properties of the organism need to be included in addition to a chemical property, such as Ko . Furthermore, many chemicals are known to bioconcentrate to a lesser extent. There is some evidence that this reduced bioaccumulation is due to a size or shape cut-off effect in membrane permeation but an exact value is difficult to set. Other reasons for lower bioconcentration factors are related to biotransformation. It is not possible yet to apply discrete equations for these kind of deviating compounds. Other descriptors will have to be developed and applied that describe the underlying processes for the deviating behaviour. Parameters which relate the size of the molecule, and also parameters that represent differences in potency for biotransformation, will be important. 

Activation of protective mechanisms occurs when the harmful substance penetrates into the body. The penetration rate of pollutants and their distribution in the body, however, as well as the range of detoxification or elimination mechanisms, is subject to anatomical, physiological, biochemical and other factors. Phase 1 biotransformation typically involves changes catalysed by hydrolases and oxidases, in which polar functional groups are... 

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