**3.1 Hepatic cytochromes P450 involved in drug metabolism**

The cytochromes P450 are terminal oxidase that comes under the superfamily of hemoproteins. This super family P450 has around 154 genes that can be seen in case of 23 eukaryotes in both plants and animal along with 6 prokaryotes. Among all the isoform of CYPP450, CYP1, CYP2 and CYP3 are known to play important roles in majority of drug metabolism. P450 are responsible for catalyzing some of the reactions such as hydroxylation, dealkylation, and oxygenation. These cytochromes also have ability to catalyze reductive reactions where the metabolite produced from the reaction leads to inactivation of P450 [16].

Most xenobiotics are eliminated from body after undergoing chemical modification. The process of chemical modification of drug can be referred as biotransformation. In the process of biotransformation, lipophilic drugs are rendered more hydrophilic so that they can be excreted easily. Biotransformation occurs through two phases namely: Phase I and Phase II. Phase I reaction is also termed as functionalization reaction whereas Phase II reaction is called as conjugation reaction. In phase I reactions, the parent compounds undergoes oxidative processes to form more polar metabolites. In some case more reactive metabolites are also produced. The Phase I reactions are broadly of three types namely oxidation, reduction and hydrolysis. In phase II reactions, the parent compound or its Phase I metabolites are conjugated with endogenous substances like sulfate, glutathione or glucuronic acids to from a more water soluble and less toxic product that easily excrete out from the body.

Examples of Phase II reactions are


Metabolism of diverse ranges of xenobiotic are carried out by enzymes such as cytochrome (CYP) and flavin monooxygenases. CYP are found in liver predominantly and are also found in organs like gastrointestinal tract (GIT), lungs and placenta. 16 gene families and 29 sub families of CYP are found in human beings. Among these families, family 1, 2 and 3 are mostly responsible for biotransformation of xenobiotic. Most abundant CYP found in liver of adult humans is CYP3A4. CYP450 are also known to express more than 2000 mutation and ultimately shows polymorphisms. Some of the CYP also shows single nucleotide polymorphism (SNP). Some important polymorphism are seen in 1A2, 2C9, 2C19 and 2D6. The

#### *Hepatocytes and Their Role in Metabolism DOI: http://dx.doi.org/10.5772/intechopen.99083*

genetic variation seen in the polymorphs are Mendelian inherited and are responsible for the catalytic variation they show in towards xenobiotic. Due to polymorphism, pharmacokinetic as well pharmacodynamics activities of drugs may show variations. When variability is seen in plasma concentration of drugs, it may lead to either toxicity due to exaggerated plasma concentration or suboptimal actions may be seen when plasma concentration is not achieved. If a new drug is metabolized by polymorphic enzyme then it can be considered as a drawback for the new drug because of the variation that can be shown to by the polymorphic enzyme [17, 18].
