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Lanosterol 14-alpha demethylase Catalase Peroxidase Lanosterol synthase Squalene monooxygenase Squalene synthase Farnesyl pyrophosphate synthase Miconazole 4,4-Dimethylcholesta- 8,14,24-trienol Miconazole Lanosterol O2 NADPH Formic acid H+ H2O NADP (S)-2,3-Epoxysqualene Squalene O2 NADPH H2O NADP Farnesyl pyrophosphate NADPH NADP PPi Farnesol NADPH PPi NADP H2O2 H2O O2 H2O O2 Heme FAD Magnesium Ergosterol Steroid Biosynthesis Heme Magnesium Miconazole inhibits the production of ergosterol by inhibiting Lanosterol 14-alpha demethylase Endoplasmic Reticulum Fungal yeast cell Bud of Fungus Cell Miconazole is applied topically to the infected area, commonly superficial skin or the vagina Fungal Cell Ergosterol is essential in maintaining membrane integrity in fungi. Without ergosterol, the fungus cell cannot synthesize membranes thereby increasing fluidity and preventing growth of new cells Inhibition of Lanosterol 14-alpha demethylase causes an accumulation of Farnesol. Farnesol is an inhibitor of drug efflux ABC transporters, namely Candida CaCdr1p and CaCdr2p. Miconazole inhibits peroxidase and catalase which leads to an accumulation of hydrogen peroxideand reactive oxygen species, which are toxic to the cell and eventually cause apoptosis. Peroxisome
Endoplasmic Reticulum ERG11 cta CCP1 ERG7 ERG1 ERG9 ERG20 Miconazole 4,4- Dimethylcholesta- 8,14,24- trienol Miconazole Lanosterol Oxygen NADPH Formic acid Hydrogen Ion Water NADP (S)-2,3- Epoxysqualene Squalene Oxygen NADPH Water NADP Farnesyl pyrophosphate NADPH NADP Pyrophosphate Farnesol NADPH Pyrophosphate NADP Hydrogen peroxide Water Oxygen Water Oxygen Ergosterol Steroid Biosynthesis