Sitosterol biosynthesis

The demonstration166 that the side-chains of 24-methylenecycloartanol (96), 24-methylenelophenol, and campesterol incorporated two deuterium atoms, whilst those of 24-ethylidenecycloartanol, stigmasterol, and sitosterol contained a maximum of four deuterium atoms when biosynthesized by cultures of barley embryo in the presence of [Me-2H3]methionine, provides further evidence for the intermediacy of 24-methylene- and 24-ethylidene-compounds in the biosynthesis of C28 and C29 phytosterols. The barley system was also able to convert labelled 24-ethylidenelophenol into radioactive sitosterol efficiently. These results, and those obtained from feeding experiments with [2-14C,(4R)-4-3Hi]MVA, are consistent with a pathway (Scheme 9) to stigmasterol (97) involving isomerization of (98) to a... 

Arthropod Sterols.—The absence of sterol biosynthesis has been observed in further examples from the class ArachnidaT The conversion of /5-sitosterol back to cholesterol was demonstrated in bees and in locusts/ where it was shown that fucosterol, but not 24-methylenecholesterol, was probably a precursor of desmosterol and cholesterol. Some interconversions of pregnane, andros-tane, and oestrane steroids have been examined in the cricket.The stages in the oxidation of the side-chain of ecdysone hormones have been studied in several species. In Calliphora, the sequence of oxidation seems to be hydroxylation at C-25, C-22,and C-20 i.e. (115)— (116)— (117)— (118). The last step, conversion... 

Sterols include 4a-methylsterols, intermediates of sterols and triterpens biosynthesis. Analysis of the sterol fraction demostrated the constant presence of P-sitosterol, campesterol and stigmasterol, A -avenasterol, while A" -avenasterol may be absent or present in very low amount. P-sitosterol makes up the 75-90% of the total sterol fraction, the rest of sterols occur in minute quantities. 

Details have been published of the biosynthesis of olean-12-ene and urs-12-ene type triterpenoids in tissue cultures of lsodon japonicus (Labiatae).10 The results are fully in accord with the original biogenetic postulates of Ruzicka and his colleagues.11 By using [5-13C, 5-2H2]MVA as substrate it was shown that, as expected, both squalene 2,3-epoxides [part structures (12) and (13)] are involved in the biosynthesis of 2a-hydroxyursolic acid (14), 3-epimaslinic acid (15), and j3-sitosterol in I. japonicus. The 13C n.m.r. spectra of (14) and (15) suggested... 

Ntanios, F. Y. and Jones, P. J. H. 1999. Dietary sitosterol reciprocally influences cholesterol absorption and biosynthesis in hamsters and rabbits. Atherosclerosis 143, 341-351. 

The structural relationship between phytosterols and BRs has been proposed from the biosynthetic points of view. All naturally occurring BRs possess carbon skeletons identical to those of common phytosterols (e.g., campesterol, 24-methylene-cholesterol, isofiicosterol, sitosterol, and cholesterol). Thus, BRs may be speculatively regarded as the enzymatic oxidation products of phytosterols with the corresponding carbon skeletons, as is the case of the biosynthesis of other steroid hormones (e.g., ecdysteroids (25) and 1,25-dihydroxyvitamin D3 (26)). Although BL has recently been proved to be biosynthesized from CS in crown gall cells of Catharanthus roseus (27), a major part of the biosynthesis of BRs is remained to be investigated. Experiments using radio-labeled precursors are required to clarify the biosynthesis of BRs in a suitable plant system. 

Arthropoda.—Steroid biosynthesis seems to be absent from all of this phylum. Examples of the class Arachnida, Diplopoda, Crustacea, and Insecta have been examined. Steroid metabolism in insects has been reviewed. " It should be borne in mind that insects can synthesise some terpenoids [e.g. (32) and (46)], but there is an absolute dietary requirement for steroids. Phytosterols such as -sitosterol are converted back into cholesterol derivatives apparently by the reverse of side chain alkylation (86 R = Et) (85 R = CHMe)—> (85 R = CHj)— (84)— (74). In addition a A -double bond is introduced. Parasites, and other organisms naturally present, may contribute to some of these reactions. ... 

Fig. 2. Biosynthesis of typical plant sterols. Boxed sterols are probable precursors of various brassinosteroids. Among these sterols, sitosterol, stigmasterol, campesterol, 24-epicampesterol and cholesterol are the most common end-of-pathway sterols in plants. Italic letters refer to the lesions in the biosynthesis mutants of Arabidopsis (dim) and pea (Ikb).

Table II also contains previously unpublished results of experiments In which medium was supplemented with AY-9944, a compound originally developed as a hypocholesterolemic agent due to Its Inhibition of the A -sterol reductase Involved In the conversion of 7-dehydrocholesterol to cholesterol In de novo sterol biosynthesis In mammals (44). In other biological sys ms (bramble suspension cells, algae an yeast), AY-9944 Inhibits A - to A -lsomerases and. In one case, a A -sterol reductase (45-47). When sitosterol-containing media was supplemented with...

In the biosynthesis of plant sterols, the side chain may be subject to further methylations, all dependent on SAM as the methyl donor. The 24a-ethyl groups found in sitosterol and stigmasterol are formed by the transfer of a methyl group to a 24-methylene sterol, which is generated as shown above the resulting Z-24-ethylidene sterol intermediate is isomerized to a A -24-ethyl sterol whose C-24(25) double bond is subsequently stereospecifically reduced by an NADPH-dependent sterol A -reductase. 

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