Sites of biotransforming enzymes (Drug Biotransformational Systems – Origins and Aims) (Human Drug Metabolism)

Aside from their biotransformational roles in steroid biosynthesis and drug/toxin clearance, CYPs carry out a wide array of metabolic activities that are essential to homeostasis. This is not surprising, as they are found in virtually every tissue. The main areas are the liver and gut that have the highest concentrations of biotransformational capability. These CYPs are mainly concerned with the processing and clearance of large amounts of various endogenous and exogenous, or ‘xenobiotic’, chemicals. The CYPs and other metabolizing systems in organs such as the lung and kidney make relatively little contribution to the overall clearance of a drug, but are relevant in the formation of toxic species from drugs and xenobiotics. The brain is a good example of this; CYPs are often found in particular areas, rather than universally distributed. They are found at very low levels, often less than 2 per cent of hepatic P450 levels. Their central nervous system (CNS) role involves catalyzing specific neural functions by regulating endogenous entities such as neurosteroids, rather than larger-scale chemical processing. A number of CYPs are also engaged in the regulation of vascular tone through arachidonic acid metabolism in the periphery as well as the brain. To date, nearly 60 human CYPs have been identified and perhaps surprisingly, about half of them have highly specific biomodulatory roles that are distinct from high volume chemical oxidation. It is likely that hundreds more CYP-mediated endogenous functions remain to be discovered.

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