Phytosterol metabolism

Ntanios, FY and Jones, PJ (1998) Effects of variable dietary sitostanol concentrations on plasma lipid profile and phytosterol metabolism in hamsters. Biochim. Biophys. Acta, 1390, 237-244. 

LING w H, JONES p J (1995) Dietary phytosterols a review of metabolism, benefits and side effects. Life Sci. 57 195-206. 

Insect steroid metabolism has two biochemically distinctive components dealkylation of phytosterols to cholesterol and polyhydroxylation of cholesterol to ecdysone. We will focus on the first of these. Lacking the ability to synthesize sterols de novo, insects instead have evolved a dealkylation pathway to convert plant sterols to cholesterol(7-10). The dealkylation pathways are apparently absent in most other higher and lower organisms, which can convert mevalonate to squalene and thence into sterols( ). Specific insecticides are possible based on these biochemical differences. 

Substitution of fluorine for hydrogen at C-25 and C-26 of phytosterols and at C-20, C-22, C-24 or C-25 of cholesterol provided compounds which did not affect Manduca sexta growth or development significantly at 50 ppm in the diet(15). In contrast, we predicted that the C-29 fluorophytosterols (Fig. 1, X=F) would release the metabolic equivalent of fluoroacetate as a result of dealkylation(, ). 

Ostlund, R.E. (2004). Phytosterols and cholesterol metabolism. Current Opinion in Lipid-ology, 15, 37 U. 

Jones, P.J., Howell, T., MacDougall, D.E., Feng, J.Y., and Parsons, W. 1998. Short-term administration of tall oil phytosterols improves plasma lipid profiles in subjects with different cholesterol levels. Metabolism 47, 751-756. 

Howell, T.J., MacDougall, D.E., and Jones, P.J., Phytosterols partially explain differences in cholesterol metabolism caused by corn or olive oil feeding, J. Lipid Res., 1998 39, 892, 1998. 

The biosynthesis of cholesterol, related steroids, and phytosterols is dealt with in this section whereas the further metabolism of these classes and the remaining nonsteroidal triterpenoids are covered in the following two sections. Reviews have appeared on the biosynthesis of sterols and higher terpenoids, the in vivo metabolism of steroids in primates" and in plant tissue culture," and dietary feedback control of cholesterol synthesis." The latter contains a reasoned defence of the hypothesis that HMG-CoA reductase is controlled by alterations to its supporting microsomal membrane. Abstracts of a symposium on all aspects of steroid biosynthesis have appeared." ... 

In order to understand the growth retardation mechanism of S-uniconazole, the shoots of Pisum sativum L. treated with S- and R-uniconazoles were analyzed in terms of the levels of the endogenous GAs, BRs, and phytosterols. Only referring to BRs, it is of interest to examine whether uniconazoles modify the biosynthesis of BRs. BRs contained in the shoots of P. sativum L. were extracted, purified, and analyzed by the GC/MS. GC/MS analysis of the active fraction led to the identification of CS m/z (rel. int.) 512 (M+, 54%), 155 (100%). GC/SIM quantitation using an internal standard (d6-CS) revealed that the content of CS in the control plants was 0.9 ng/g fir. wt. and, after treatment with S- and / -uniconazoles, reduced to 54% and 34% of the controls, respectively. The result suggests that the altered metabolism of BRs is likely to be involved in the action mechanism of S-uniconazole. 

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. ... 

A variety of steroidal natural products have been isolated from insects, even though, as mentioned previously, insects are not able to carry out de novo steroid biosynthesis. The steroidal nucleus, as it occurs in insect primary and secondary metabolites thus must ultimately come from dietary or symbiotic microbial sources. For many phytophagus insects, C28 and C29 phytosterols are converted into cholesterol (C27) through a series of dealkylation pathways, with cholesterol subsequently serving as the starting point for further metabolic transformations, and resulting in a wide variety of steroid-based natural products. In other cases, dietary phytosterols are sequestered and deployed unmodified, and as with other compound classes, the relative importance of dietary sequestration versus modification is not always clear. 

As discussed above, phytophagous insects generally are capable of converting dietary C2g- and C29-phytosterols to cholesterol. However, several kinds of insects which show unusual variations in the utilization and metabolism of dietary phytosterols were found recently by Svoboda et al. [165-172]. 

The effect of 22-dehydrocholesterols (97) on the growth of Drosophila was investigated by Kirchner et al. [180]. cis- and /ran5-22-dehydrocholesterols were added to media of diet for 10 species of Drosophila. The cis isomer prevented normal maturation of 4 species and the trans isomer was toxic to 9. These findings were corroborated by tests with 4 representative species on a sterol-deficient medium under axenic conditions. Addition of cholesterol to the latter overcame the toxicity of the trans isomer. trans-22-Dehydrocholesterol may be acting as a competitive inhibitor in the metabolism of phytosterols to cholesterol or ecdysone by the insects. 

It has become increasingly evident that considerable variability in steroid utilization and metabolism exists among phytophagous species of insects. In recent years, we have discovered several phytophagous species that are unable to convert C28 or C29 phytosterols to cholesterol. This Includes one species that dealkylates the C-24 substituent of the side chain but produces mostly saturated sterols and several species that totally lack the ability to dealkylate the sterol side chain. Certain members of this latter group are of particular interest because they have adapted to utilizing a Cos sterol as an ecdysteroid precursor and makisterone A (C28) has been identified as the major ecdysteroid of certain developmental stages of these species. 

Coleoptera. The confused flour beetle, Tribollum confusum, was the first phytophagous insect we found that produces an appreciable amount of a sterol other than cholesterol from radiolabeled dietary C28 and C29 phytosterols. We found this insect produced large quantities of 7-dehydrocholesterol, equivalent to as much as 70% of the total tissue sterols isolated (12). It was further determined that cholesterol and 7-dehydrocTfolesterol were in equilibrium in this flour beetle. Another new intermediate, 5,7,24-cholestatrien-3B-ol was identified as an intermediate between desmosterol and 7-dehydrocholesterol (Figure 3). We found very similar pathways of sterol metabolism to exist in the closely related flour beetle, Tribolium castaneum (13). However, another flour beetle, Tenebrio moHtor, nad only about one-third or less of the levels of 7-dehydrocholesterol as the two Tribolium species, but still much higher levels of this sterol than has been found in most species. Fucosterol 24,28-epoxide was also implicated as an intermediate in the synthesis of cholesterol from sitosterol in T. mol i tor (14). 

Coleoptera. Sterol metabolism studies with another important stored products pest, the khapra beetle, Trogoderma granarium, revealed another phytophagous Insect that is unable to dealkylate and convert C28 and C29 phytosterols to cholesterol (23). Similar results were obtained whether a diet consisting of cracked wheat and brewer s yeast or an artificial diet coated with radiolabeled sterols was used (24). There was some selective uptake of cholesterol from tFe dietary sterols, as indicated by an enrichment of cholesterol in the pupal sterols 1.2% of total), compared to the dietary sterols (0.5% of total). Unlike the previously discussed stored product coleopteran pests, T. confusum and T. castaneum, both of which had high levels of 7-dehycTrochoiesterol, Tfo 7-dehydrocholesterol could be identified in the sterols from the khapra beetle. 

Hymenoptera. While examining the effects of various dietary sterols on brood production in honey bees. Apis mellifera, we discovered that the honey bee utilized dietary C28 and (igg phytosterols unchanged (25,26). Regardless of the dietary sterol added to a chemically-deTTneJ diet, or even with no sterol added, 24-methylenecholesterol was always the major sterol of the next generation of bees, and sitosterol and isofucosterol were also present in appreciable amounts. Detailed studies with either radiolabeled campesterol, sitosterol, or 24-methy1 enecholesterol added to the artificial diet provided no evidence for the metabolism of any of these phytosterols to cholesterol or other sterols (27). 

---