Sterol numbering system

Sterols (from the Greek (rr pe6s meaning solid) are complex solid alcohols found in the unsaponifiable lipid fraction from the tissues of most animals and many plants. The principal, but by no means the only sterol of the vertebrates, is cholesterol, the structural formula of which, together with the conventional numbering system, is shown... 

In this chapter, we have examined the use of cells and enzymes to chemically transform lipids. We have had to be selective and have predominantly focused attention on the transformation of sterols and steroids. We first explained why these compounds were commercially important and why they only occur in low concentrations in natural systems. We pointed out that a very large number of reaction types are possible, but those which have found greatest use include stereospedfic hydroxylations, alcohol/ketone interconversion, hydrolysis, conjugation and isomerisation. 

Point mutations that give altered sterol profiles have been generated in A. thaliana and S. cerevisiae LSs. Matsuda and co-workers used a yeast expression system to select for spontaneous mutations in A. thaliana CS that restored sterol-independent growth to an LS-deficient mutant of yeast [67]. In this way they were able to identify a mutation from isoleucine to valine (at Ile481) that allowed synthesis of the sterols lanosterol and parkeol. Further studies have identified a number of other amino acid residues in A. thaliana CS and... 

The full extent to which saponins reduce cholesterol absorption requires further study. Because of the large number of saponins present in the food supply, it is possible that all of the mechanisms discussed earlier contribute to reduced cholesterol absorption. Unlike plant sterols in which their mode of action is relatively well defined, there are probably multiple effects of saponins within the intestinal tract, including their ability to interact with other dietary constituents and the ability of some saponins to be absorbed systemically. The regulatory effects of saponins on cellular cholesterol transport have not been examined. 

The sterol cholesterol (Fig. 2b) is a major constituent of animal plasma membranes but is absent from prokaryotes. The fused ring system of cholesterol means that it is more rigid than other membrane lipids. As well as being an important component of membranes, cholesterol is the metabolic precursor of the steroid hormones (see Topic K5). Plants contain little cholesterol but have instead a number of other sterols, mainly stigmasterol and P-sitosterol which differ from cholesterol only in their aliphatic side chains. 

These sterol sulfate esters show activity in a number of enzyme and receptor-binding assays and are also active in the anti-HIV screen run at the US National Cancer Institute. A dereplication scheme for this class of compounds has been published by Cardellina et al. (36), in which extracts are chromatographed in three systems Sephadex G-25 for molecular weight C4 wide pore (300) and CIS narrow pore (60 A). Fractions are assayed against HIV and the patterns of activity compared to that observed for halistanol sulfate. Sterol sulfates from six sponge extracts were eluted with methanol H20 (2 1 v/v) and allowed for the rapid dereplication of this class of compound. In... 

The stoichiometry of the polyene antibiotic—cholesterol interaction has been measured in various systems with different techniques. The filipin—cholesterol interaction has been the subject of extensive study and the results suggest this interaction is equimolar. The data on other polyenes is not so definite, but suggests that only a small number of sterol molecules interact with one polyene antibiotic molecule. 

Plant hormone biosynthesis and metabolism are influenced and modified, too, as already mentioned, by a large number of typical secondary plant constituents of quite different structures (Eef. 5, 6). For instance, it has been shown that some oi-disubstituted acetic acid derivatives are active both as antiauxins and as inhibitors of the biosynthesis of cyclic terpenoids. Thus, some more simple model compounds synthesized by ourselves, for example substituted a-phenoxy-isobutyrio acids, are not only competitive auxin inhibitors but they are also able to inhibit both the gibberellin and sterol biosynthesis. The same is true for some well known plant growth retardants, such as CCO or AMO 1618, which are inhibitors of gibberellin biosynthesis both in plants and in Fus ium moniliforme, but at the same time they are inhibiting and modifying also the biosynthesis of steroids in the respective organisms as well as in animal in vitro systems (Eef. 29) ... 

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