Introduction

The exposure to a vast array of xenobiotics (foreign chemicals from sources such as drugs, food additives, cigarette smoke, cosmetics and various natural products) is frequent and inevitable and depending on their toxicity, xenobiotic elimination from the body system is crucial. Since many xenobiotics that penetrate cell membranes are lipophilic, chemical modifications that render them more hydrophilic are necessary for effective removal via the urine, for example. For toxic hydrophilic compounds, modifications that make them more inert are equally important. The biological catalysts responsible for these chemical modifying processes are known as the drug metabolising enzymes (DMEs).

These enzymes have activities with characteristics like a double-edged sword, catalyzing pathways that make xenobiotics more active in addition to deactivation processes described above. A generalized scheme representing this dual role is illustrated in Figure 1. The formation of reactive intermediates [ 1 ] although rare, has led to DNA binding and has been linked with various carcinomas of the bladder [2,3] and colon [4], among others. Biotransformations catalysed by the DMEs are also responsible for the generation of metabolites for the needed pharmacology in the case of pro-drugs. Each pathway is subject to variations in dietary, genetic and environmental impacts which govern the efficacy and toxicity of xenobiotics. It is well accepted that the study of xenobiotic interaction with these DMEs is the prudent approach to gaining a mechanistic insight into and avoiding adverse effects associated with numerous xenobiotics.

DRUG, NP, FOREIGN CHEMICAL

Organs Liver, Kid

Organs Liver, Kid

"BIOTRANSFORMATH METABOLISM BY DMEs

FURTHER BIOACTIVITY

Inactive metabolite

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