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Lanosterol 14 alpha-demethylase
==Introduction==
Lanosterol 14 α-demethylase (or CYP51A1) is a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol.〔"Metabocard for 4,4-Dimethylcholesta-8,14,24-trienol (HMDB01023)." Human Metabolome Database. Web. 25 Feb. 2014. .〕 The cytochrome P450 isoenzymes are a conserved group of proteins that serve as key players in the metabolism of organic substances and the biosynthesis of important steroids, lipids, and vitamins in eukaryotes.〔Lepesheva, Galina I., and Michael R. Waterman. "Sterol 14α-Demethylase Cytochrome P450 (CYP51), a P450 in All Biological Kingdoms." ''Biochim Biophys Acta''. 2008. 1770(3): 467-77.〕 As a member of this family, lanosterol 14 α-demethylase is responsible for an essential step in the biosynthesis of sterols. In particular, this protein catalyzes the removal of the C-14 α-methyl group from lanosterol (Lepesheva et al.). This demethylation step is regarded as the initial checkpoint in the transformation of lanosterol to other sterols that are widely used within the cell (Lepesheva et al.).
Although lanosterol 14 α-demethylase is present in a wide variety of organisms, this enzyme is studied primarily in the context of fungi, where it plays an essential role in mediating membrane permeability.〔Daum G, Lees ND, Bard M, Dickson R. "Biochemistry, Cell Biology and Molecular Biology of Lipids of Saccharomyces cervisiae". ''Yeast''. 1998. 14(16):1471-1510.〕 In fungi, CYP51 catalyzes the demethylation of lanosterol to create an important precursor that is eventually converted into ergosterol (Lepesheva et al.). This steroid then makes its way throughout the cell, where it alters the permeability and rigidity of plasma membranes much as cholesterol does in animals.〔Becher, Rayko, and Stefan G. R. Wirsel. "Fungal Cytochrome P450 Sterol 14α-demethylase (CYP51) and Azole Resistance in Plant and Human Pathogens." ''Applied Microbiology and Biotechnology.'' 2012. 95(4): 825-40.〕 Because ergosterol constitutes a fundamental component of fungal membranes, many antifungal medications have been developed to inhibit 14 α-demethylase activity and prevent the production of this key compound (Becher et al.).
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