Sterol C-5 desaturase (SC5D)

Sterol C-5 desaturase (SC5D), also known as lathosterol oxidase in humans or Erg3 in fungi, is a membrane-bound enzyme located in the endoplasmic reticulum that catalyzes the introduction of a C5-C6 double bond into sterol intermediates. In humans, it performs the penultimate step of cholesterol biosynthesis by converting lathosterol to 7-dehydrocholesterol, a precursor to both cholesterol and vitamin D [4, 11]. In fungi and protozoa like Leishmania, it is essential for the production of ergosterol, the primary sterol required for membrane integrity and fluidity [1, 31]. Mutations in the human SC5D gene cause lathosterolosis, a rare autosomal recessive disorder characterized by developmental delays, microcephaly, and liver disease [8, 13]. In clinical microbiology, SC5D is a critical factor in drug resistance; its inactivation allows fungal pathogens to survive azole treatment by preventing the formation of toxic sterol diols, and it also reduces the binding affinity of polyene antibiotics like amphotericin B [2, 6, 31]. While few direct clinical inhibitors exist, SC5D is an emerging target in oncology due to its role in the SC5D-7-DHC axis, which regulates ferroptosis by protecting cell membranes from lipid peroxidation [24, 30].

Other names

Lathosterol oxidase3beta-hydroxysteroid-delta5-desaturaseDelta(7)-sterol 5-desaturaseSC5DLS5DESERG3LSOLathosterol 5-desaturase

Direct inhibition of sterol C-5 desaturase activity; indirect interaction via pathway-mediated production of toxic sterol diols (azoles) or reduction of polyene binding sites (amphotericin B).