Lanosterol 14α-demethylase

Lanosterol 14α-demethylase (also known as CYP51A1) is a cytochrome P450 enzyme that is involved in the biosynthesis of steroids and sterols. This enzyme is responsible for the removal of the 14α-methyl group from lanosterol, a critical step in the production of cholesterol in animals and ergosterol in fungi.

Function

Lanosterol 14α-demethylase is a key enzyme in the biosynthetic pathway that produces cholesterol in animals and ergosterol in fungi. The enzyme catalyzes the demethylation of lanosterol, converting it into 4,4-dimethylcholesta-8,14,24-trien-3β-ol. This reaction is a crucial step in the production of cholesterol or ergosterol, which are essential components of cellular membranes.

Structure

The structure of lanosterol 14α-demethylase is characterized by a heme prosthetic group, which is typical of cytochrome P450 enzymes. The enzyme also contains a conserved cysteine residue that coordinates to the heme iron. The active site of the enzyme is located in a hydrophobic pocket, which accommodates the lanosterol substrate.

Clinical significance

Inhibition of lanosterol 14α-demethylase is a common strategy for the treatment of fungal infections. Many antifungal drugs, such as azoles, work by inhibiting this enzyme, thereby disrupting ergosterol biosynthesis and compromising the integrity of the fungal cell membrane. Mutations in the gene encoding lanosterol 14α-demethylase can lead to resistance to these antifungal drugs.

In humans, mutations in the CYP51A1 gene, which encodes lanosterol 14α-demethylase, have been associated with congenital cataracts and Antley-Bixler syndrome, a rare disorder characterized by skeletal and craniofacial abnormalities.

See also

• Cytochrome P450
• Steroid biosynthesis
• Azole

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