Sterol delta 14-reductase (ERG24)

Sterol delta 14-reductase, encoded by the ERG24 gene, is a key enzyme in the fungal ergosterol biosynthesis pathway. It catalyzes the NADPH-dependent reduction of the C-14 double bond in sterol intermediates, such as 4,4-dimethylcholesta-8,14,24-trienol, to form 4,4-dimethylzymosterol (1.4.2). Ergosterol is a vital component of the fungal cell membrane, where it regulates fluidity, permeability, and the activity of membrane-bound proteins (1.3.4). Inhibition of this enzyme by drugs like morpholines (e.g., amorolfine) results in the depletion of ergosterol and the accumulation of aberrant sterols like ignosterol, which disrupt membrane integrity and inhibit fungal growth (1.2.3, 1.3.1). While essential for growth in many fungi, its inhibition also significantly reduces virulence and increases sensitivity to other drugs in species like Candida albicans (1.2.5). Currently, therapeutic use is primarily limited to topical treatments for superficial mycoses due to potential systemic toxicity and cross-reactivity with mammalian sterol metabolism (1.2.2, 1.3.1).

Other names

Delta 14-sterol reductaseC-14 sterol reductaseErg24pDelta(14)-sterol reductaseC-14 reductaseFungal Delta 14-reductase

Inhibition of the reduction of the C-14 double bond in sterol intermediates, leading to ergosterol depletion and accumulation of abnormal sterols like ignosterol, which disrupts fungal cell membrane integrity.