Ergosterol

1.04

Small hydrated plates from alcohol, in hydrated needles from ether. The best crystalized form contains 1 1/2 mol H2O

Platelets from water, alcohol; needles from ethyl ether

Colorless crystals

Slightly soluble in ethanol, ethyl ether, petroleum ether; soluble in benzene, chloroform

One gram dissolves in 660 mL alcohol, in 45 mL boiling alcohol, in 70 mL ether, in 39 mL boiling ether, in 31 mL chloroform.

16 mg/mL

250 °C at 0.01 mm Hg

170

170 °C

MP: 168 °C. Complete removal from water is almost impossible and results in an amorphous mass, melting range 166-183 °C. ... Precipitated by digitonin. Affected by light and air, turns yellow. Oxygen forms peroxides and hydrogen may form polyhydro compounds.

170 °C

Plates or needles, mp 169-171 °C. Specific optical rotation: -71 deg at 23 °C/D ( c = 1.1 in CHCl3), -88 deg at /546 (CHCl3) /Benzoate/

UV irradiation gives vitamin D4 ... Solvated needles from ethyl acetate + methanol, mp 152-153 °C (dried). Specific optical rotation: -109 deg at 19 °C/D (CHCl3); also reported as needles from chloroform-methanol, mp 128-130 °C; Specific optical rotation: -121 deg at 19 °C/D ( c = 0.1). UV max: 262,272,282,294 nm (epsilon 8000, 11200, 11800, 6800). /22,23-Dihydro analog/

Specific optical rotation: -135 deg (in chloroform)

Specific optical rotation: -135 deg at 20 °C/D ( c = 1.2 in CHCL3, calcd as anhydr); -171 deg at 20 °C/546

Solid; Turns yellow on exposure to light and air; [Merck Index] Hygroscopic solid; [Sigma-Aldrich MSDS]

Solid

AFFECTED BY LIGHT & AIR & TURNS YELLOW

201.01 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；204.57 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

MP: 157-158 °C; Specific optical rotation: -75 deg at 19 °C/D ( c = 2.1 in CHCl3) /22,23-Dihydro acetate/

A plant sterol widely distributed in nature

This chemical does not meet GHS hazard criteria for 2.1% (1 of 47) of reports.

Danger

H300 (12.8%): Fatal if swallowed [Danger Acute toxicity, oral]；H413 (85.1%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]

P264, P270, P273, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 47 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 47 reports by companies.；There are 2 notifications provided by 46 of 47 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Status: Active Update: 27-09-2016 https://echa.europa.eu/registration-dossier/-/registered-dossier/18145

Ergosterol: Does not have an individual approval but may be used under an appropriate group standard

May cause irritation; [Sigma-Aldrich MSDS] See Vitamin D.

Aquatic Chronic 4 (85.1%)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

MURINE LEUKEMIA CELLS (L1210) GROWN IN MEDIUM CONTAINING ERGOSTEROL (40 UG/ML) THEN EXPOSED BRIEFLY TO AMPHOTERICIN B (0-10 UG/ML) WERE MORE SENSITIVE TO THE ANTIBIOTIC THAN WERE CONTROLS.

AFTER 4-HR GROWTH PERIOD IN PRESENCE OF 5X10-9 MOLES KETOCONAZOLE, ACETATE INCORPORATION INTO ERGOSTEROL BY CANDIDA ALBICANS WAS INHIBITED APPROXIMATELY 50%.

INHIBITION OF ERGOSTEROL BIOSYNTHESIS IN CANDIDA ALBICANS BY THE ANTIFUNGAL AGENT MICONAZOLE NITRATE WAS INVESTIGATED AFTER IN VITRO CONTACT WITH THE DRUG FOR 1, 4, 16, & 24 HR.

The functions and biosynthesis of sterols have been effective targets for fungal control in different areas, including pharmaceutical and agricultural applications. Fungi are among the organisms that synthesize sterols, principally ergosterol. In this paper, the effect of dibutyryl-cAMP (db-cAMP) on ergosterol level and the interaction of drugs that would change the concentration of cAMP with antifungal drugs have been investigated. Sterols were extracted from Candida albicans, and ergosterol was measured using the gas chromatography method. The interaction of different agents was measured by the broth dilution method. It was found that phosphodiesterase inhibitors reverse the inhibitory activity of azole antifungal drugs. Evaluating the ergosterol level of C. albicans incubated with db-cAMP revealed that it increased ergosterol level. Further experiments provided evidence attributing the observed interaction between azoles and phosphodiesterase inhibitors to the relationship between ergosterol and cAMP. The possible significance of this interaction includes potentiation of antifungal activity of drugs by manipulating the cAMP level.

For more Interactions (Complete) data for ERGOSTEROL (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+6(SRC), determined from a structure estimation method(2), indicates that ergosterol is expected to be immobile in soil(SRC). Volatilization of ergosterol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.6X10-4 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Ergosterol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). However, adsorption to soil is expected to attenuate volatilization(SRC). The soil microbe Nocardia erthopolis was able to grow on ergosterol(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+6(SRC), determined from a structure estimation method(2), indicates that ergosterol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.6X10-4 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 9 hours and 11 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 2.1X10+4 years if adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 1,600(SRC), from an estimated log Kow of 8.86(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Aquatic biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ergosterol, which has an estimated vapor pressure of 1.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ergosterol may be removed from the air by wet or dry deposition(SRC). When irradiated with uv light, ergosterol develops powerful vitamin D2 activity(5) and therefore the compound is expected to be susceptible to direct photolysis by sunlight(SRC).

Vitamin D is excreted into breast milk in limited amounts. A direct relationship exists between maternal serum levels of vitamin D and the concentration in breast milk. Chronic maternal ingestion of large doses may lead to greater than normal vitamin D activity in the milk and resulting hypercalcemia in the infant. /Vitamin D/

/AQUATIC SPECIES/ In crustaceans, cholesterol is an essential nutrient, which they must directly obtain from their food or by bioconversion from other dietary sterols. Eukaryotic phytoplankton contain a great variety of sterols that differ from cholesterol in having additional substituents or different positions and/or number of double bonds in the side chain or in the sterol nucleus. ... This study ... investigated to what extent these structural features affect the growth and reproduction of Daphnia galeata in standardized growth experiments with the cyanobacterium Synechococcus elongatus supplemented with single sterols as food source. The results indicated that delta 5 (sitosterol, stigmasterol, desmosterol) and delta 5.7 (7-dehydrocholesterol, ergosterol) sterols meet the nutritional requirements of the daphnids, while the delta 7 sterol lathosterol supports somatic growth and reproduction to a significantly lower extent than cholesterol. Dihydrocholesterol (delta 0) and lanosterol (delta 8) did not improve the growth of D. galeata, and growth was ad versely affected by the delta 4 sterol allocholesterol. Sterols seem to differ in their allocation to somatic growth and reproduction. Thus, structural differences of dietary sterols have pronounced effects on life-history traits of D. galeata.

The ergosterol weighted-average concentration in fungal spores commonly encountered in subtropical ambient air was 0.191 pg/spore(1). The ergosterol content in 20 white-rot fungi isolates ranged from 2,380 to 13,060 ug/g fungal biomass, with Bjerkandera adusta 4,312, Coriolopsis gallica 8,260, and Phanerochaete chyrosporium 3,642 ug/g fungal biomass reported as examples(2). Ergosterol content was shown to be affected negatively by the amount of pollutants present(2). Ergosterol has also been identified in a variety of fungi associated with food spoilage molds(3).

Ergosterol concentrations in digested sludges collected from four French municipal wastewater treatment plants in Lyon (Saint Fons, 11/18/1993) and Paris (Asnieres/Oise, 8/26/1991; Acheres, 1/26/1993; Evry 6/8/1993) were at <0.1, <0.1, <0.1, and 0.02 mg/g dried matter, respectively(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ergosterol can be estimated to be 2.5X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that ergosterol is expected to be immobile in soil.

Ergosterol is a plant sterol that is widely distributed in nature(1). Twelve species and strains of fungal spores and yeast cells commonly found in the subtropical ambient air as well as mold spores(3) were shown to contain ergosterol(2).

RURAL/REMOTE: The ergosterol concentration in subtropical air from an unspecified location was estimated as approximately 230 pg/sq m(SRC), based upon the weighted-average concentration in fungal spores commonly encountered in subtropical ambient air of 0.191 pg/spore(1).

/SIGNS AND SYMPTOMS/ Initial...symptoms of vitamin D toxicity are...associated with hypercalcemia and consist in weakness, fatigue, lassitude, headache, nausea, vomiting, and diarrhea. Early impairment of renal function...manifest by polyuria, polydipsia, nocturia, decreased urinary concentrating ability and proteinuria. /Vitamin D/

/SIGNS AND SYMPTOMS/ With prolonged hypercalcemia there may be deposition of calcium salts in soft tissues, most significantly within kidney.../resulting/ in nephrolithiasis, diffuse nephrocalcinosis, or both. Other sites of calcification may include blood vessels, heart, lungs, and skin. /Vitamin D/

/SIGNS AND SYMPTOMS/ Some individuals exhibit hypertension. ...Changes in blood chemistry are elevated concentrations of plasma calcium and nonprotein nitrogen; phosphate concentrations are variable. Mobilization of calcium from bone contributes to hypercalcemia and is...responsible for...osteoporosis in...hypervitaminosis D. /Vitamin D/

/SIGNS AND SYMPTOMS/ Vitamin D toxicity may be manifested in fetus. There is...relationship between excess maternal vitamin D intake or extreme sensitivity to vitamin and nonfamilial congenital supravalvular aortic stenosis. In infants, this anomaly is often found...with other stigmata of hypercalcemia. /Vitamin D/

For more Human Toxicity Excerpts (Complete) data for ERGOSTEROL (12 total), please visit the HSDB record page.

Ergosterol's production and use as a vitamin and pharmaceutical intermediate(1) may result in its release to the environment through various waste streams(SRC).

AEROBIC: The soil microbe Nocardia erthopolis was able to grow on ergosterol(1).

Status: Active Update: 27-09-2016 https://echa.europa.eu/registration-dossier/-/registered-dossier/18145

Ergosterol: Does not have an individual approval but may be used under an appropriate group standard

STATE OF DEFICIENCY: ...RESULTS IN INADEQUATE ABSORPTION OF CALCIUM & PHOSPHATE. CONSEQUENT DECR IN PLASMA CALCIUM STIMULATES PARATHYROID HORMONE SECRETION...RESTORE PLASMA CALCIUM AT EXPENSE OF BONE CALCIUM. ...RICKETS...OSTEOMALACIA...LIKELY...DURING PREGNANCY OR LACTATION. /VITAMIN D/

... A new member of the F-box family, Pof14, which forms a canonical, F-box dependent SCF (Skp1, Cullin, F-box protein) ubiquitin ligase complex /is described/. The Pof14 protein has intrinsic instability that is abolished by inactivation of its Skp1 interaction motif (the F-box), Skp1 or the proteasome, indicating that Pof14 stability is controlled by an autocatalytic mechanism. Pof14 interacts with the squalene synthase Erg9, a key enzyme in ergosterol metabolism, in a membrane-bound complex that does not contain the core SCF components. pof14 transcription is induced by hydrogen peroxide and requires the Pap1 transcription factor and the Sty1 MAP kinase. Pof14 binds to and decreases Erg9 activity in vitro and a pof14 deletion strain quickly loses viability in the presence of hydrogen peroxide due to its inability to repress ergosterol synthesis. A pof14 mutant lacking the F-box and an skp1-3 ts mutant behave as wild type in the presence of oxidant showing that Pof14 function is independent of SCF. This indicates that modulation of ergosterol level plays a key role in adaptation to oxidative stress.

The continuous use of triazoles can result in the development of drug resistance. Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus fumigatus have been documented. The azoles block the ergosterol biosynthesis pathway by inhibiting the enzyme 14-alpha-demethylase, product of the CYP51. Fungal azole resistance involves both amino acid changes in the target site that alter drug-target interactions and those that decrease net azole accumulation. The reduced intracellular accumulation has also been correlated with overexpression of multidrug resistance (MDR) efflux transporter genes of the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) classes. About 20 genes are involved in the A. fumigatus ergosterol biosynthesis pathway. There are several duplicated genes in this pathway. Interestingly, erg3 and erg11 showed two copies in A. fumigatus. In general, Aspergillus spp. have proportionally more MFS transporter encoding genes than Saccharomyces cerevisiae, S. pombe, and Neurospora crassa. The drug H+ (12 and 14 spanners) sub-families are also proportionally greater than in the other species. Although the numbers of ABC transporter encoding genes are comparable, again the Aspergillus spp. have more ABC transporters related to multidrug permease than the other fungal species.

The human pathogen Candida albicans is responsible for a large proportion of infections in immunocompromised individuals, and the emergence of drug-resistant strains is of medical concern. Resistance to antifungal azole compounds is often due to an increase in drug efflux or an alteration of the pathway for synthesis of ergosterol, an important plasma membrane component in fungi. However, little is known about the transcription factors that mediate drug resistance. In Saccharomyces cerevisiae, two highly related transcriptional activators, Upc2p and Ecm22p, positively regulate the expression of genes involved in ergosterol synthesis (ERG genes). ... A homologue in C. albicans of the S. cerevisiae UPC2/ECM22 genes ... named ... UPC2 /has been identified/. Deletion of this gene impaired growth under anaerobic conditions and rendered cells highly susceptible to the antifungal drugs ketoconazole and fluconazole. Conversely, overexpression of Upc2p increased resistance to ketoconazole, fluconazole, and fluphenazine. Azole-induced expression of the ERG genes was abolished in a Delta upc2 strain, while basal levels of these mRNAs remained unchanged. Importantly, the purified DNA binding domain of Upc2p bound in vitro to putative sterol response elements in the ERG2 promoter, suggesting that Upc2p increases the expression of the ERG genes by directly binding to their promoters. These results provide an important link between changes in the ergosterol biosynthetic pathway and azole resistance in this opportunistic fungal species.

Ergosterol, a typical fungal sterol, induced in tobacco (Nicotiana tabacum L. cv. Xanthi) suspension cells the synthesis of reactive oxygen species and alkalization of the external medium that are dependent on the mobilization of calcium from internal stores. ... Specific inhibitors /were used/ to elucidate the signal pathway triggered by ergosterol compared with cryptogein, a proteinaceous elicitor of Phytophthora cryptogea. Herbimycin A and genistein, inhibitors of tyrosine protein kinases, had no effect on the oxidative burst and pH changes induced by both elicitors. Similarly, H-89, an inhibitor of protein kinase A, had no effect on the induction of these defense reactions. However, the response to both elicitors was completely blocked by NPC-15437, a specific inhibitor of animal protein kinase C (PKC). The responses induced by cryptogein but not those induced by ergosterol were inhibited by U73122 and neomycin, inhibitors of phospholipase C (PLC). On the other hand, the activity of phospholipase A2 (PLA2) measured using a fluorogenic substrate was stimulated by ergosterol and not by cholesterol and cryptogein. A specific inhibitor of PLA2, arachidonic acid trifluoromethyl ketone (AACOCF3), inhibited the pathway stimulated by ergosterol but not that induced by cryptogein. These results suggest that the cryptogein-induced signal pathway leading to the oxidative burst and DeltapH changes includes PLC and PKC, whereas this response induced by ergosterol includes PLA2 and PKC.

For more Mechanism of Action (Complete) data for ERGOSTEROL (7 total), please visit the HSDB record page.

... The metabolism of ergosterol by cytochrome P450scc /is demonstrated/ in either a reconstituted system or isolated adrenal mitochondria. The major reaction product was identified as 17alpha,24-dihydroxyergosterol. Purified P450scc also generated hydroxyergosterol as a minor product, which is probably an intermediate in the synthesis of 17alpha,24-dihydroxyergosterol. In contrast to cholesterol and 7-dehydrocholesterol, cleavage of the ergosterol side chain was not observed. NMR analysis clearly located one hydroxyl group to C24, with evidence that the second hydroxyl group is at C17. 17alpha,24-Dihydroxyergosterol inhibited cell proliferation of HaCaT keratinocytes and melanoma cells. Thus, in comparison with cholesterol and 7-dehydrocholesterol, the 24-methyl group and the C22-C23 double bond of ergosterol prevent side chain cleavage by P450scc and change the enzyme's hydroxylase activity from C22 and C20, to C24 and C17, generating bioactive product.

In order to investigate the effect of the different stereochemistry of C-24 on the microbial C-26 oxidation of sterol side-chain the genetically modified Mycobacterium sp. BCS 396 strain was used to transform erogsterol. Ergosterol was converted to 3-oxo-4,22-ergostadien-26-oic acid methyl ester, 3-oxo-1,4,22-ergostatrien-26-oic acid methyl ester, and 3-oxo-1,4,22-ergostatrien-26-oic acid, the structures of which have been determined by IR, 1H NMR, 13C NMR, and mass spectroscopy. The X-ray structure of 3-oxo-4,22-ergostadien-26-oic acid methyl ester revealed that oxidation at C-26 of the ergostane side-chain generates a chiral center with S-configuration at C-25 as a result of chiral induction of the C-24 center.

The results of experiments on rats given the ergosterol-containing diet for a long time indicate that ergosterol was incorporated in liver tissues in trace amounts which are not comparable with ergosterol concentrations exerting an effect in model experiments. Ergosterol was not detected in the liver after 3-day experiments. At the same time it was established that the proportion of unchanged ergosterol in rat feces was about 16% of the amount administered per os. The products of a possible ergosterol transformation (dehydroneoergosterol-24-methyl-1,3,5 (10), 6,8 (9), 22-hexaen-3 beta-ol; 24-methylcholesta-7,24 (28)-dien-3 beta-ol; 4-cholesta-7,22,25 (?)-trien-3 beta-ol; 4-methylcholesta-7,22 (?)-dien-3 beta-ol, and so forth were identified in feces.

Metabolism of orally administered ergosterol (Erg) ... in rats and ... vitamin D biological activity were investigated. Most of orally administered Erg ... /was/ excreted in feces and the remaining sterols were absorbed through intestine. The absorbed sterols were not transported in skin as the intact forms but metabolized into brassicasterol and cholesterol, respectively, within 25 hr. Neither increment of intestinal calcium absorption nor plasma calcium concentrations were observed by oral administration of Erg ... to vitamin D-deficient rats...

The chick-oviduct assay was used to investigate the effects of dietary ergosterol on the response to oral progestogens and estrogens. Progestogens alone had no effect on the oviduct but the hypertrophy due to estrogen was greatly enhanced by simultaneous treatment with progestogen at all dose levels tested. Ergosterol had no effect on any of the responses of the oviduct studied.

Precursor forms of vitamins.

Vitamin D is excreted into breast milk in limited amounts. A direct relationship exists between maternal serum levels of vitamin D & the concn in breast milk. Chronic maternal ingestion of large doses may lead to greater than normal vitamin D activity in the milk & resulting hypercalcemia in the infant. /Vitamin D/

The results of experiments on rats given the ergosterol-containing diet for a long time indicate that ergosterol was incorporated in liver tissues in trace amounts which are not comparable with ergosterol concentrations exerting an effect in model experiments. Ergosterol was not detected in the liver after 3-day experiments. At the same time it was established that the proportion of unchanged ergosterol in rat feces was about 16% of the amount administered per os. The products of a possible ergosterol transformation (dehydroneoergosterol-24-methyl-1,3,5 (10), 6,8 (9), 22-hexaen-3 beta-ol; 24-methylcholesta-7,24 (28)-dien-3 beta-ol; 4-cholesta-7,22,25 (?)-trien-3 beta-ol; 4-methylcholesta-7,22 (?)-dien-3 beta-ol, and so forth were identified in feces.

Extracellular；Membrane

Most important provitamin D, usually obtained from yeast; Used as a vitamin; [Merck Index] Used as a vitamin and to make vitamin D2 and cortisone; [HSDB]

CHEM INT FOR VITAMIN D2

Antirachitic vitamin; when irradiated with UV light, it has vitamin D activity; source of estradiol.

Used in commercial production of cortisone

THERAP CAT: Vitamin (antirachitic)

Ergosterol is an evolutionary precursor of cholesterol and is the major sterol present in lower eukaryotes.

The best crystalline form contains 1 1/2 molecules of water ...

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) GREATER THAN 4.54X10+5 GRAMS

ESSENTIALLY 100% AS A CHEM INT FOR VITAMIN D2 (1976)

EXTRACTION OF TOTAL FAT FROM YEAST, SAPONIFICATION, REEXTRACTION OF THE UNSAPONIFIABLE PORTION WITH ETHER, FOLLOWED BY DRYING & RECRYSTALLIZATION

Usually obtained from yeast which synthesizes it from simple sugars such as glucose. Damp yeast yields about 2.5% ergosterol, the variety of yeast being very important.

Isoln procedure: Green et al, US pat 3,006932 (1961 to Vitamins Ltd.)

Synthesized by yeast from simple sugars, obtained from fungus ergot.

Cosmetics -> Undefined function

Usually obtained from yeast which synthesizes it from simple sugars such as glucose. Damp yeast yields about 2.5% ergosterol, the variety of yeast being very important.