Sterol 14-demethylase

Although the lanosterol 14α-demethylase is present in a wide variety of organisms, the enzyme is studied primarily in the context of fungi, where it plays an essential role in mediating membrane permeability.

[3] Because ergosterol constitutes a fundamental component of fungal membranes, many antifungal medications have been developed to inhibit 14α-demethylase activity and prevent the production of this key compound.

The demethylated products of the CYP51 reaction are vital intermediates in pathways leading to the formation of cholesterol in humans, ergosterol in fungi, and other types of sterols in plants.

Seeking new means to treat such infections, drug researchers have begun targeting the 14α-demethylase enzyme in fungi; destroying the fungal cell's ability to produce ergosterol causes a disruption of the plasma membrane, thereby resulting in cellular leakage and ultimately the death of the pathogen (DrugBank).

[3] These compounds bind as the sixth ligand to the heme group in CYP51, thereby altering the structure of the active site and acting as noncompetitive inhibitors.

[3] Coordination of azoles to the prosthetic heme group in the enzyme's active site causes a characteristic shift in CYP51 absorbance, creating what is commonly referred to as a type II difference spectrum.