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.

Vitamin D in Nature: A Product of Synthesis and/or Degradation of Cell Membrane Components.

Abstract: The review discusses the data on vitamin D accumulation in animals, plants, and other organisms. 7-Dehydrocholesterol (7-DHC) and ergosterol are considered to be the only true precursors of vitamin D, although even vitamin D2 (ergocalciferol) is not fully comparable to vitamin D3 (cholecalciferol) in regard to their functions. These precursors are converted by UV radiation into the corresponding D vitamins. There are a few published reports that this reaction can also occur in the dark or under blue light, which is unexpected and requires explanation. Another unexpected result is conversion of pro-vitamins D (7-DHC and ergosterol) into vitamin D3 and D2 via pre-vitamin D at low temperatures (<16°C) in the lichen Cladonia rangiferina. An extensive survey of literature data leads to the conclusion that vitamin D is synthesized from (1) 7-DHC via lanosterol (D3) in land animals; (2) 7-DHC via cycloartenol (D3) in plants; (3) ergosterol via lanosterol (D2) in fungi; and (4) 7-DHC or ergosterol (D3 or D2) in algae. Vitamin D primarily accumulates in organisms, in which it acts as a pro-hormone, e.g., land animals. It can also be found as a degradation product in many other species, in which spontaneous conversion of some membrane sterols upon UV irradiation leads to the formation of vitamins D3 or D2, even if they are not necessarily needed by the organism. Such products accumulate due to the absence of metabolizing enzymes, e.g., in algae, fungi, or lichens. Other organisms (e.g., zooplankton and fish) receive vitamins D with food; in this case, vitamins D do not seem to carry out biological functions; they are not metabolized but stored in cells. A few exceptions were found: the rainbow trout and at least four plant species that accumulate active hormone calcitriol (but not vitamin D) in relatively high amounts. As a result, these plants are very toxic for grazing animals (cause enzootic calcinosis). In connection with the proposal of some scientists to produce large quantities of vitamin D with the help of plants, the accumulation of calcitriol in some plants is discussed.

A comparison of cycloartenol and lanosterol biosynthesis and metabolism by the Oomycetes

Abstract: Representative members in each of the four orders of Oomycetes (Phytophthora cactorum, Peronosporales;Lagenidium callinectes, L. giganteum, Lagenidiales;Saprolegnia ferax, Saprolegniales;Apodachylella completa, Leptomitales) have been examined for their ability to synthesize and polycyclize squalene-oxide (SO) to a tetracyclic product and to differentiate between cycloartenol and lanosterol metabolism to sterols.P. cactorum andL. giganteum failed to synthesize or metabolize SO, cycloartenol or lanosterol. While the other three fungi synthesized sterols via SO and lanosterol, a minor metabolism of added cycloartenol to the 4,4-desmethyl-14α-methylcyclosteroid dehydropollinastanol was observed.

Protein engineering of oxidosqualene-lanosterol cyclase into triterpene monocyclase.

Abstract: A computational modeling/protein engineering approach was applied to probe H234, C457, T509, Y510, and W587 within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase (ERG7), which spatially affects the C-10 cation of lanosterol formation. Substitution of Trp587 to aromatic residues supported the “aromatic hypothesis” that the π-electron-rich pocket is important for the stabilization of electron-deficient cationic intermediates. The Cys457 to Gly and Thr509 to Gly mutations disrupted the pre-existing H-bond to the protonating Asp456 and the intrinsic His234:Tyr510 H-bond network, respectively, and generated achilleol A as the major product. An H234W/Y510W double mutation altered the ERG7 function to achilleol A synthase activity and generated achilleol A as the sole product. These results support the concept that a few-ring triterpene synthase can be derived from polycyclic cyclases by reverse evolution, and exemplify the power of computational modeling coupled with protein engineering both to study the enzyme's structure–function–mechanism relationships and to evolve new enzymatic activity.

Lanosterol oligosaccharides from the plants of the subfamily scilloideae and their antitumor-promoter activity

Abstract: Phytochemical studies of the bulbs of Scilla peruviana, Eucomis bicolor, Chionodoxa gigantea and C. luciliae gave respectively two new and two known, four new and two known, three known, and one new and five known lanosterol oligosaccharides. The structures of the new compounds were determined from spectroscopic data. A total of 19 lanosterols, including previously isolated compounds, were examined for inhibitory activity on 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated 32P incorporation into phospholipids of HeLa cells as the primary screening test to find new antitumor-promoter compounds.