Sterol-C5-desaturase (SC5D)

Sterol-C5-desaturase (SC5D) is a highly conserved membrane-bound enzyme in the cholesterol biosynthesis pathway, catalyzing the conversion of lathosterol to 7-dehydrocholesterol. This step is critical in mammals for membrane sterol homeostasis and steroid biosynthesis. Mutations in SC5D cause lathosterolosis, an autosomal recessive inborn error of cholesterol metabolism characterized by multiple congenital abnormalities, mental retardation, and liver dysfunction. In fungi, such as yeast, the ortholog ERG3 is required for ergosterol synthesis—a target for azole antifungal drugs. Loss-of-function mutations in fungal ERG3 can confer resistance to azoles by circumventing toxic sterol accumulation, although its clinical significance in pathogenesis and therapy remains under debate. SC5D is therefore an important molecule both as a diagnostic biomarker for rare cholesterol biosynthesis disorders and as a driver of antifungal resistance in pathogens.

Other names

Lathosterol oxidaseSC5DLERG3S5DESDelta(7)-sterol 5-desaturaseDelta(7)-sterol 5(6)-desaturaseDelta(7)-sterol C5(6)-desaturaseSterol-C5-desaturase-like3β-hydroxysteroid-Δ5-desaturaseLathosterol 5-desaturase

In fungi, loss or mutation of ERG3 (C5SD) confers resistance to azole antifungals by preventing the accumulation of toxic sterols when the pathway is blocked upstream. Pharmacological targeting of upstream cholesterol pathway enzymes can impact SC5D function indirectly. SC5D inhibitors are not standard clinical agents; its role is more diagnostic or a genetic disease marker than a direct therapeutic target in humans.