Ergosterol (ergosta-5,7,22-trien-3β-ol) is a
sterol
Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...
found in
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s of
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
and
protozoa
Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
, serving many of the same functions that
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
serves in
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s. Because many fungi and protozoa cannot survive without ergosterol, the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s that synthesize it have become important targets for
drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.
Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...
. In human nutrition, ergosterol is a
provitamin A provitamin is a substance that may be converted within the body to a vitamin. The term previtamin is a synonym.
The term "provitamin" is used when it is desirable to label a substance with little or no vitamin activity, but which can be converted ...
form of
vitamin D2; exposure to
ultraviolet
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...
(UV) light causes a chemical reaction that produces
vitamin D2.
Role in fungi
Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in fungi, and named for
ergot, the common name of members of the fungal genus ''
Claviceps'' from which ergosterol was first isolated. Ergosterol is a component of
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
and other
fungal
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s, serving many of the same functions that cholesterol serves in animal cells.
Its specificity in higher fungi is thought to be related to the climatic instabilities (highly varying humidity and moisture conditions) encountered by these organisms in their typical ecological niches (plant and animal surfaces, soil). Thus, despite the added energy requirements of ergosterol synthesis (if compared to cholesterol), ergosterol is thought to have evolved as a nearly ubiquitous, evolutionarily advantageous fungal alternative to cholesterol.This advantage could be linked to the presence of two conjugated double bonds in the structure (B-ring) of ergosterol giving it antioxidant properties.
Target for antifungal drugs
Because ergosterol is present in cell membranes of fungi, yet absent in those of animals, it is a useful target for
antifungal drugs. Ergosterol is also present in the cell membranes of some protists, such as
trypanosomes. This is the basis for the use of some antifungals against West African
sleeping sickness
African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...
.
Amphotericin B
Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...
, 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
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
and
hydrons) 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
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to pr ...
,
miconazole
Miconazole, sold under the brand name Monistat among others, is an antifungal medication used to treat ring worm, pityriasis versicolor, and yeast infections of the skin or vagina. It is used for ring worm of the body, groin (jock itch), and ...
,
itraconazole
Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mo ...
,
clotrimazole
Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock i ...
, and
myclobutanil
Myclobutanil is a triazole chemical used as a fungicide. It is a steroid demethylation inhibitor, specifically inhibiting ergosterol biosynthesis. Ergosterol is a critical component of fungal cell membranes.
Stereoisomerism
Safety
The Safet ...
work in a different way, inhibiting synthesis of ergosterol from
lanosterol
Lanosterol is a tetracyclic triterpenoid and is the compound from which all animal and fungal steroids are derived. By contrast plant steroids are produced via cycloartenol.
Role in biosynthesis of other steroids
Elaboration of lanosterol under en ...
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
inhibit
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotr ...
the enzyme that performs these
demethylation Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen at ...
steps in the biosynthetic pathway between lanosterol and ergosterol.
[
]
Target for antiprotozoal drugs
Some protozoa, including ''Trichomonas
''Trichomonas'' is a genus of anaerobic excavate parasites of vertebrates. It was first discovered by Alfred François Donné in 1836 when he found these parasites in the pus of a patient suffering from vaginitis, an inflammation of the vagina. ...
'' and ''Leishmania
''Leishmania'' is a parasitic protozoan, a single-celled organism of the genus '' Leishmania'' that are responsible for the disease leishmaniasis. They are spread by sandflies of the genus ''Phlebotomus'' in the Old World, and of the genus '' ...
'' are inhibited by drugs that target ergosterol synthesis and function
As a vitamin D2 precursor
Ergosterol is a biological precursor of vitamin D2, the chemical name of which is ergocalciferol
Ergocalciferol, also known as vitamin D2 and nonspecifically calciferol, is a type of vitamin D found in food and used as a dietary supplement. As a supplement it is used to prevent and treat vitamin D deficiency. This includes vitamin D defici ...
. Exposure of white button mushrooms to UV-C irradiation at 0.403 mW per cm2 intensity from 30 cm distance produced time-dependent increases in vitamin D2 concentrations.
This happens naturally to a certain extent, and many mushrooms are irradiated after harvest to increase their vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
content. Fungi are also grown industrially so that ergosterol can be extracted and converted to Vitamin D for sale as a dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
and food additive
Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (salt ...
.[
Preparations of irradiated ergosterol containing a mixture of previtamin and vitamin D2 were called ''viosterol'' in the 1930s.
]
Toxicity
Ergosterol powder is an irritant to skin, eyes, and the respiratory tract. Ingestion of large amounts can cause hypercalcemia, which (if prolonged) can lead to calcium salt deposits in the soft tissues and kidneys.
See also
* Mushrooms and vitamin D
References
{{Phytosterols
Sterols
Nutrition
Cell biology
Vitamin D