Biotransformation enzyme adaptation

In the course of evolution and during the short life-span of every human being, it was - and still is - necessary for the performance of enzyme systems involved in biotransformation to adapt permanently to the requirements of life. This enzyme adaptation is achieved by four mechanisms ... 

Early biological effects Initial reactions towards the presence of contaminants Defence mechanisms are a special case of early biological effects. They are either adaptive or defensive reactions and do not represent actual toxic damage. Extrusion of chemicals outside cells by protein pumps Induction of metal-binding proteins or biotransformation enzymes for elimination... 

Figure 2.16 (a) Keyelementsin bioprocessing (b) frequency of use of enzymes in biotransformations. Source adapted from Faber [145],... 

Viewed from this angle, a rise in y-GT is a physiological process, i. e. a criterion for increased enzyme induction or a sign of adaptation to the requisite (and accomplished) enhancement in biotransformation performance. 

Generally, the formation of toxic metabolites is not the only pathway of biotransformation, and the overall metabolism is constituted toward detoxication and bioactivation processes. The toxic metabolites are themselves often further detoxified. The duality between a beneficial detoxication phenomenon (metabolism, drug resistance) and the occurrence of a toxic effect represents the cost for adaptability of metabolic enzymes to the diversity of xenobiot-ics. For those interested, a recent review applies the above chemistry to predict drug safety. 

The wide array of enzyme families, subfamilies, and isoforms that mediates xenobiotic biotransformations serves as an important defense mechanism to protect the body against a dazzling variety of xenobiotic insults. Nebert (University of Cincinnati Medical Center) once drew a broad parallel between the immune system and the drug metabolizing enzymes, noting that both systems are adaptive and are capable of protecting the body against diverse molecular species. 

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