Desmethyl sterols

The methyltransferase that catalyses the formation of 24-ethylidene sterols from 24-methylene precursors in bean rust uredospores (Uromyces phaseoli) can also alkylate lanosterol, 24-methylenecholesterol, zymosterol, and desmosterol to produce C29 sterols.[28- H]-24-Methylenecholesterol was efficiently (ca. 3% yield) incorporated into withaferin A (88) and withanolide D (89) by Withania somnif-era, whereas [28- H]-24-methylcholesterol did not act as a precursor in this system. However, since feeding experiments with [28- H]-24-methylcholesta-5,24-dien-3/8-ol gave ambiguous results it was not possible to rule out other 4-desmethyl sterols (with C28) as intermediates in withanolide biosynthesis. 

Plant sterols, also called phytosterols, have been reported to include over 250 different sterols and related compounds in various terrestrial and marine materials (Akihisa et al., 1991). Sitosterol, stigmasterol, and campesterol are the commonly consumed plant sterols. The predominant sterol class in vegetable oils is 4-desmethyl sterols. Sitosterol usually contributes more than 50% of desmethyl sterols. The other most significant desmethyl sterols include campesterol, stigmasterol, A5-avenasterol, A7-avenasterol, and A7-stigmastenol. Brassicasterol is a typical sterol for rapeseed and other Cruciferae. Stanol occurs in significant amounts in com bran and fiber oil (Piironen, et al., 2000). 

Sterols are another class of compounds which have been used to understand the processes controlling transport of biologically produced materials in seawater. There are many species-specific sources of sterols in the ocean, although few, if any, species of bacteria biosynthesize 4-desmethyl sterols. Thus, the interpretation of seawater sterol profiles is somewhat less complicated than similar studies with compounds important in bacterial metab-... 

To determine sterols, a portion of the total lipid extract is saponified using methanolic potassium hydroxide, and sterols subsequently recovered in 2 1 hex-ane/chloroform. The sterols are converted to the corresponding trimethylsilyl (TMS) ethers using bis-N,0-(trimethylsilyl)trifluoroacetamide, BSTFA, and analyzed by capillary GC and GC with mass spectrometry. Reviews of relative retention times and mass spectra for sterol TMS ethers have been published [e.g. 73]. In some cases, sterol acetates, rather than TMS ethers, are the derivatives prepared for GC. SiHca column chromatography of the total lipid extract may also be used instead of saponification to isolate the sterol fraction [74], or even sterol subclasses such as 4,4-dimethyl, 4-monomethyl and 4-desmethyl sterols [75], prior to derivatization. However, this approach only includes free sterols in the analysis, whereas by saponifying the total extract, sterols present as steryl esters are also detected. 

Desmethyl sterols, with no methyl group at C-4, are the main class of sterols in plants and thus in the human diet. The proportion of 4-desmethyl sterols among total sterols in common crude vegetable oils is >85% (Piironen et al, 2000a). Sitosterol, the principal sterol in most plants, is usually accompanied by its 22-dehydro analogue, stigmasterol. The molecular stmctures of the most important plant sterols and stands (see Section B.5 below) are shown in... 

Cholesterol is also a 4-desmethyl sterol, and the similarity between its ring structure and the substitution at C-24 to those of some plant sterols (Figure 3) seem to be critical elements for the important effects of plant sterols on cholesterol absorption. Only 4-desmethyl sterols (not 4-methyl or 4,4-dimethyl sterols) exert this effect. 

Methyl sterols occur naturally in only minor amounts as they are precursors of the desmethyl sterols. In commercial soybean sterols, 98.1% are 4-desmethyl sterols, 1.3% are 4-methyl sterols and 0.6% are 4,4-dimethyl sterols (Sierksma et al, 1999). Compared with 4-desmethyl sterols, the number of different 4-methyl sterol compounds is small. 

Figure 4. Molecular structures of campesterol (a 4-desmethyl sterol) and a-amyrin (a triterpene...

Small amounts of sitostanol and campestanol, which are 5,6-saturated analogues of the main 4-desmethyl sterols (sitosterol and campesterol), occur in plant materials such as coniferous trees (pine, spruce) and certain grains (rye, wheat and corn/maize). 

Table 2. Absorption of certain 4-desmethyl sterols of interest to functional foods before and during sitostanol ester margarine consumption ...

Plant sterols (phytosterols), especially 4-desmethyl sterols, have recently gained much scientific and commercial interest due to the introduction of plant sterol-enriched foods and dietary supplements with marked serum cholesterollowering efficacy. Due to the structural similarity between cholesterol and 4-desmethyl plant sterols, the intake of optimal amounts of plant sterols and stanols (saturated sterols) lowers intestinal cholesterol absorption and results in a 6-15% reduction in semm LDL cholesterol concentrations. 

Plant sterols and stanols can be classified on the basis of structure or biosynthesis. Only the 4-desmethyl sterols and stanols affect cholesterol absorption and decrease semm total and LDL cholesterol levels, suggesting that similarity of ring structure and side-chain length are cmcial requirements for their effects on cholesterol absorption. 

Desmethyl sterols decrease serum cholesterol concentrations by interfering with cholesterol absorption. Plant sterols and stanols reduce the solubility of cholesterol in the micellar phase, thus reducing the amount of cholesterol available for absorption. Furthermore, some still-unknown mechanisms at the absorptive sites of the intestinal enterocytes or within the enterocytes also play a role in the overall effect of plant sterols on cholesterol absorption. 

Figure 2. Moleeular struetures of examples from the three main sterol sub-elasses sitosterol, a 4-desmethyl sterol with no methyl group at C-4 gramisterol, a 4-monomethyl sterol and eyeloartenol, a 4,4-dimethyl sterol.

Figure 3. Molecular structures of the most important 4-desmethyl sterols and stanols.

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