Squalene epoxidase, function

Mechanism of Action. Terbinafine inhibits a specific enzyme (squalene epoxidase) that is responsible for sterol synthesis in the fungal cell membrane. This action impairs cell wall synthesis, with subsequent loss of cell membrane function and integrity. Inhibition of this enzyme causes squalene to accumulate in the fungal cell, which can also impair cell function and lead to death of the fungus. 

The Opening of Squalene-2,3-Epoxide Steroids are tetracyclic compounds that serve a wide variety of biological functions, including hormones (sex hormones), emulsifiers (bile acids), and membrane components (cholesterol). The biosynthesis of steroids is believed to involve an acid-catalyzed opening of squalene-2,3-epoxide (Figure 14-6). Squalene is a member of the class of natural products called terpenes (see Section 25-8). The enzyme squalene epoxidase oxidizes squalene to the epoxide,... 

Formation of sterols from squalene involves cyclization. First a microsomal mixed-function oxidase (squalene epoxidase) forms squalene-2,3-oxide in the presence of NADPH, FAD and O2 (there is no requirement for cytochrome P450 in this reaction). The cyclization of the oxide to lanosterol then takes place by a concerted reaction without the formation of any stable intermediates. This conversion, which has been described as the most complex known enzyme-catalysed reaction, depends on a cyclase with a molecular mass of only 90kDa. In plants and algae squalene-2,3-epoxide is cyclized to cycloartenol which is the precursor of stigmasterol whereas lanosterol is the precursor of cholesterol and ergosterol (Figure 7.19). 

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