14demetilasi

14demetilasi, commonly referred to as 14α-demethylation, is a biochemical reaction in sterol biosynthesis that removes a methyl group at the carbon-14 position of a sterol precursor. In most eukaryotes, the principal substrate is lanosterol, and the reaction converts it into a later-stage sterol such as zymosterol. The step is essential for producing mature sterols like cholesterol in animals and ergosterol in fungi.

The reaction is catalyzed by the enzyme lanosterol 14α-demethylase, a cytochrome P450 enzyme often designated CYP51. This enzyme is associated with the endoplasmic reticulum and requires molecular oxygen and NADPH. The mechanism involves hydroxylation of the 14α-methyl group, followed by oxidative fragmentation that releases formaldehyde and yields a demethylated sterol. The overall transformation reduces the number of methyl groups at the C14 position, enabling further processing toward end-state sterols.

Biological significance varies by organism but is broadly conserved in eukaryotes. In mammals, 14α-demethylation is a key step in cholesterol biosynthesis; in fungi, it is part of ergosterol production, which is vital for membrane structure. Because of its central role, the enzyme is a target for azole antifungal drugs, which inhibit CYP51 and disrupt ergosterol synthesis, impairing fungal growth. Resistance can arise from mutations or altered expression of the enzyme.

Overall, 14demetilasi represents a critical enzymatic step that enables the maturation of sterols, affecting membrane properties and the physiology of diverse organisms.