Ergosterol in fungi

Cholesterol is the sterol characteristic of animal cells plants, fungi, and protists make other, closely related sterols instead. They use the same synthetic pathway as far as squalene 2,3-epoxide, at which point the pathways diverge slightly, yielding other sterols, such as stigmasterol in many plants and ergosterol in fungi (Fig. 21-37). 

The branched isoprene unit, which is also synthesized from the C, pool, is the basic structure of terpenoids. Less condensed structures are used as volatile pheromones, e.g., jasmonic acid, menthol, or camphor, or as natural rubber material. More condensed structures such as steroids and hopanoids are part of membranes, influencing their fluidity. They are also highly specific to their source organisms. Best known are cholesterol (in animals and plants), ergosterol (in fungi), and brassicasterol (in diatoms). Besides cellulose, hopanoids are the most abundant biomolecules. 

Semisynthetic y0-lactam antibiotics with a 1,2,4-triazolyl substituent have been prepared and are in clinical use. However, the most important application of 1,2,4-triazoles is as biocides. 3-Amino-1,2,4-triazole (amitrole, amizol) is an unselective herbicide. Triadimenol 4 is one of the most effective fungicides. Its configuration IS, 2R) is essential for its action [162]. The 1,2,4-triazole fungicides inhibit the biosynthesis of ergosterol in fungi. 

It is important to the performance of AMPs that they be efficient in killing bacteria and other pathogens but leave human cells unaffected. The basis for such selectivity is that membranes of bacteria and human cells have different compositions. For example, cholesterol is rich (up to about 45%) in human cell membranes, while it is replaced by ergosterol in fungi and absent in bacteria. There are also differences in phospholipid composition. For example, PC and SM are abundant in the outer layer of erythrocytes, which renders these essentially uncharged. In contrast, the outer membrane of bacteria is rich in anionic lipids, such as phosphatidylglycerol (PG), cardiolipin,... 

Like the a2ole derivatives, it inhibits the biosynthesis of ergosterol. However, naftifine [65472-88-0] does not inhibit the cytochrome P-450 dependent C-14-demethylase, but the epoxidation of squalene. Squalene epoxidase cataly2es the first step in the conversion of squalene via lanosterol to ergosterol in yeasts and fungi or to cholesterol in mammalian cells. The squalene epoxidase in C. albicans is 150 times more sensitive to naftifine, C2 H2 N, than the en2yme in rat fiver (15). Naftifine is available as a 1% cream. 

Terbinafine Inhibits epoxidation of squalene in fungi increased levels are toxic to them Reduces ergosterol prevents synthesis of fungal cell membrane Mucocutaneous fungal infections Oral t duration, days Toxicity Gastrointestinal upset, headache, hepatoxicity t Interactions None reported... 

In fungi, ergosterol, synthesised from acetyl-CoA, is the major sterol (Figure 4.2 Mercer2) and has an essential role in the maintenance of membrane function such that a reduction in its availability disrupts membrane integrity. 

Lee, C., Howarth, R., and Howes, B. (1980). Sterols in decomposing Spartina alternijlora and the use of ergosterol in estimating the contribution of fungi to detrital nitrogen. Limnol. Oceanogr. 25,290—303. 

Nonetheless, the most fascinating and complex lipid type is sterols. They have a rigid steroid ring stmcture, which is a simple hydroxyl group as their polar head and a short flexible tail at the other end of the molecule. Of the many sterols found, two sterols exist whose significance in cells is above the others. Cholesterol is abundant in eukaryotic cells, and ergosterol is abundant in fungi. The reasons why nature has chosen these two specific sterols are not well understood. One is tempted to think that the properties of all sterols should be similar,... 

Ketoconazole is an effective antifungal agent by virtue of its capacity to block sterol/steroid s)mthesis (ergosterol in the case of fungi). In man it inhibits steroid s)mthesis in gonads and adrenal cortex and it has been used in Cushing s syndrome and prostatic cancer. 

Ergosterol (precursor ol D2) occurs naturally in fungi and yeast. Eggs and butter contain vitamin D2 (eigocalciferol) or D.1 (cholecalciferol). Milk and bread are fortiried with vitamin D2- Cholecalciferol is found in flsh liver oils. 

The ergosterol (45) biosynthesis in fungi and leishmania utilizes squalene (41) as starting material, which is obtained from long chain precursors like farnesyl pyrophosphate (39) and presqualene pyrophosphate (40). Epoxidation of squalene in the presence of squalene epoxidase furnishes squalene epoxide (42), which is succes-... 

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