Lanosterol

About: Lanosterol is a research topic. Over the lifetime, 1239 publications have been published within this topic receiving 36737 citations. The topic is also known as: (3β)-lanosta-8,24-dien-3-ol & (3β,20R)-lanosta-8,24-dien-3-ol.

Anti-Candida Drugs — The Biochemical Basis for Their Activity

Abstract: The past years have seen a continuous effort toward the synthesis of new antifungal agents. Most of them belong to the N-substituted imidazoles and triazoles. Another interesting series of antifungals are the allylamines. Biochemically, both the azole derivatives and the allylamines belong to the class of ergosterol biosynthesis inhibitors and thus differ from the polyene macrolide antibiotics. Indeed, it is now believed that the antifungal action of the polyenes, nystatin and amphotericin B, is due to a direct interaction with ergosterol itself. A more detailed analysis of the ergosterol biosynthesis inhibitors revealed that ergosterol depletion is the consequence of the interaction of the azole derivatives, e.g., miconazole, ketoconazole, and itraconazole, with the cytochrome P-450 involved in the 14 alpha-demethylation of lanosterol. Both the accumulation of 14 alpha-methylsterols and the concomitant decreased ergosterol content affect the membranes and membrane-bound enzymes of yeast and fungi. The allylamines seem to act by inhibition of the squalene epoxidase resulting in ergosterol depletion and accumulation of squalene. The target for the fluorinated pyrimidine, flucytosine, is completely different. Its antifungal properties may result from its conversion to 5-fluorouracil. The latter is then phosphorylated and incorporated into RNA, thus disrupting the protein synthesis in the yeast cell. These different biochemical targets for the antifungals of use in candidosis are discussed in this paper.

Effects of cholesterol on sodium-potassium ATPase ATP hydrolyzing activity in bovine kidney

Abstract: The (Na+,K+)-ATPase ATP hydrolyzing activity from rabbit kidney medulla basolateral membrane vesicles was studied as a function of the cholesterol content of the basolateral membranes The cholesterol content of the membranes was modified by incubation with phospholipid vesicles When the cholesterol content was increased above that found in the native membrane, the (Na+,K+)-ATPase ATP hydrolyzing activity was inhibited When the cholesterol content was decreased from that found in the native membranes, the (Na+,K+)-ATPase ATP hydrolyzing activity was inhibited Analogous effects were found with the K+-activated phosphatase activity of the same membrane vesicles Therefore, at low cholesterol contents, cholesterol was stimulatory, and at high cholesterol contents, cholesterol was inhibitory The structural specificity of this effect was tested by introducing lanosterol and ergosterol as 50% of the membrane sterol Ergosterol was the least effective at supporting (Na+,K+)-ATPase ATP hydrolyzing activity, while lanosterol was more effective, but still not as effective as cholesterol