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Ergosterol (ergosta-5,7,22-trien-3β-ol) is a mycosterol found in of fungus and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the that synthesize it have become important targets for drug discovery. In human nutrition, ergosterol is a provitamin form of ergocalciferol; exposure to ultraviolet (UV) light causes a chemical reaction that produces ergocalciferol.
Preparations of irradiated ergosterol containing a mixture of previtamin and vitamin D2 were called viosterol in the 1930s.
Amphotericin B, an antifungal drug, targets ergosterol. It binds physically to ergosterol within the membrane, thus creating a polar pore in fungal membranes. This causes ions (predominantly potassium and protons) and other molecules to leak out, which will kill the cell. Amphotericin B has been replaced by safer agents in most circumstances, but is still used, despite its side effects, for life-threatening fungal or protozoan infections.
Fluconazole, miconazole, itraconazole, clotrimazole, and myclobutanil work in a different way, inhibiting synthesis of ergosterol from lanosterol by interfering with 14α-demethylase. Ergosterol is a smaller molecule than lanosterol; it is synthesized by combining two molecules of farnesyl pyrophosphate, a 15-carbon-long terpenoid, into lanosterol, which has 30 carbons. Then, two methyl groups are removed, making ergosterol. The "azole" class of antifungal agents enzyme inhibitor the enzyme that performs these demethylation steps in the biosynthetic pathway between lanosterol and ergosterol.
The safety data sheets for ergostrol commonly confuse it with ergocalciferol (vitamin D2), which due to having vitamin D activity is hazadarous in relatively small amounts, being able to cause hypercalcemia via Vitamin D toxicity. Historical cases of poisoning are attributed to irradiated ergosterol, which contains vitamin D2 in addition to ergosterol. These do not constitute evidence for ergosterol toxicity.
Ergosterol added to a high-fat, high-sugar (HFHS) rat diet at a very high concentration of 1% increases the blood levels of vitamin D2 by about 4 ng/mL, suggesting that ergosterol that enters the mammalian skin is converted to D2 when exposed to light. This same treatment approximately quartered the serum levels of D3 and halfed the serum levels of 25-OH D3. At this dose ergosterol has a significant effect on sterol metabolism. It fully normalizes blood markers related to bile acid metabolism to control levels compared to the group only fed the HFHS diet. It displayed significant (but insufficient to match control) normalization of LDL-C and TBA levels.
Target for antiprotozoal drugs
Some protozoa, including Trichomonas and Leishmania are inhibited by drugs that target ergosterol synthesis and function
Safety
Ergosterol powder is a mechanical irritant to skin, eyes, and the respiratory tract. Ingestion may cause gastrointestinal irritation with vomiting, nausea, and diarrhea.
Toxicity
Ergosterol itself has no vitamin D activity and does not cause poisioning via this mechanism. Ergosterol added to rat food at 1% dry weight did not cause toxic effects. Ergosterol is not classifiable under GHS or REACH.
Metabolism
Ergosterol is converted to brassicasterol in the mammalian liver by DHCR7, the enzyme responsible for producing 7-dehydrocholesterol (provitamin D3) from cholestrol. Here the enzyme catalyzes an reaction analogous to the reverse of provitamin D3 production.
See also
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