The formed can be activated, inactivated, or

The liveris the primary metabolic organ. Metabolism of xenobiotics results in their ownactivation/inactivation or induction/inhibition of other xenobiotics metabolism.

The metabolic rate of an individual is greatly influenced by the geneticpolymorphisms and the co-existence of physiological conditions (Shargel and Yu,2007). Individuals are regarded as rapid metabolizers when metabolism takesplace very rapidly and higher doses of a drug/compound are required to achievea pharmacological action. Whereas, poor metabolizers are individuals thatrequire lower doses of the same compound to achieve the same pharmacologicaleffect. These individuals are more susceptible to toxicity events due to slowmetabolic rates. Unfortunately, certain factors reduce the metabolic capacityof an individual.

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For instance, aging reduces the ability to perform phase Imetabolism by approximately 30% due to the reduced organ blood perfusion. Also,existence or co-existence of cardiovascular (CVSD), Hepatic, or renal diseasereduces blood perfusion to the liver reduces metabolic and excretory rate whichincreases the occurrence of toxic effects (MSD Manual Professional Edition,2017).Xenobioticsundergo two types of biotransformation processes in the body; namely phase Iand phase II metabolic reactions. Phase I reactions are referred to asFunctionalization or degradation reactions. While phase II reactions are knownas derivatization or synthetic reactions. Generally,phase I reactions transform drugs into more polar forms. These reactions aremediated by microsomal enzymes i.e.

CYP450 enzymes, alcohol dehydrogenase,aldehyde dehydrogenase, and mono amine oxidases (MAO). Microsomal enzymes canbe found in most body cells but are mainly localized in the liver cells. Figure1. Shows the three types of phase I metabolic reactions (Shargel, Wu-Pong and Yu, 2004). CYP450enzymes work in conjunction with NADPH-CYP450 reductase that donates oneelectron to provide energy for the enzyme to perform its function. Aspreviously mentioned, phase I reactions are known as functionalizationreactions; as they convert xenobiotics into polar compounds via theintroduction of polar functional groups. Polar groups added include -OH, -SH,-NH2, and -COOH.

Metabolites formed can be activated, inactivated,or unchanged forms of the xenobiotic. The decrease in Phase I metabolismprolongs the half-life (t1/2) of drugs and other compounds. Figure 2represents the CYP450 microsomal system (Mittal et al.,2015). Phase IImetabolism is regarded as derivatization reactions that convert xenobioticsinto more polar forms which eases their excretion.

Phase II metabolism may ormay not be preceeded with phase I metabolism. Also, phase II metabolism is thelast step in the detoxification reactions (Shargel and Yu, 2007). Enzymesinvolved include transferases.

Transferases implicated with phase II metabolisminclude methyltransferases, sulfutransferases, N-acetyltransferases,glucuronosyltransferase, and GSH-transferases etc. These enzymes aremicrosomal, non-microsomal, and mitochondrial enzymes. The metabolites producedare usually inactive, highly polar, and water-soluble compounds with highmolecular weight (Mittal et al.



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