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P450 Week 1 Lab Report

Decent Essays

3. Biological Functions of Microsomal Cytochrome P450
3.1. Elimination of Xenobiotics
Xenobiotics are relatively small, non-nutrient compounds that are exogenous to the species in question (Ioannides 2002). Accordingly, xenobiotics include drugs and environmental factors, such as pollutants, pesticides and natural occurring chemicals, such as plant alkaloids (Ioannides 2002). Naturally, xenobiotics are constantly entering the body, which responds back by elimination processes, namely excretion and metabolism, to limit the exposure to xenobiotics (Ioannides 2002). Metabolism aim to alter the chemical structure of xenobiotics by wide array of biological reactions mostly enzyme mediated, leading to increase the hydrophilicity of xenobiotics, and …show more content…

Xenobiotic metabolism is usually divided to phase I and II, where polar function groups are unmasked or introduced to the chemical structure (phase I or activation), followed by the conjugation between the xenobiotic and endogenous molecules, notably glucuronic acid, to further improve hydrophilicity (phase II or conjugation) (Golan 2012). Hepatic microsomal P450 are the enzymes that dominate the catalysis of phase I metabolism of xenobiotics (Table 1 and 2) (Anzenbacher and Anzenbacherova 2001). Therefore, …show more content…

For example, although the unesterified form of AA is in nM range in blood (Brash 2001), in the other tissues the unesterified AA concentration has been reported to be remarkably higher, for example ~13-44 µM in umbilical cord and intervillous space (Benassayag, Mignot et al. 1997), ~19 µg/g (approximately equivalent to 60 µM) in skin (Hammarstrom, Hamberg et al. 1975), and ~75 µg/g (approximately equivalent to 250 µM) in liver (Edpuganti and Mehvar 2013). Therefore, in several published studies investigating P450-mediated AA metabolism in vitro, 50-100 µM of AA was deemed to be mimicking the in vivo situation (Xu, Falck et al. 2004, Imaoka, Hashizume et al. 2005). Noteworthy, in response to stimuli, the release of the free AA has been reported to be remarkably increased (Buczynski, Dumlao et al. 2009). The unesterified AA is then metabolized into several biologically active metabolites, termed eicosanoids, by one of three groups of enzymes: cyclooxygenases, lipoxygenases, or microsomal P450 enzymes (Buczynski, Dumlao et al.

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