Oxidized sterols

Assuming that the toxic compounds are able to accumulate in the body, there are certain types of products which represent potential hazards. Three types of chemical compounds as well as the radiation itself have been tabbed for possible carcinogenicity (H2) (a) branching in fatty-acid carbon chains, (b) fatty acids with odd number of carbons, (c) oxidized sterols. 

Appelqvist, L.-A. 1996. Oxidized sterols. Bulletin 315, International Dairy Federation, Brussels, pp. 52-58. 

As shown in Figure 2-23, oil breakdown during frying can be caused by oxidation and thermal alteration. Oxidation can result in the formation of oxidized monomeric, dimeric, and oligomeric triglycerides as well as volatile compounds including aldehydes, ketones, alcohols, and hydrocarbons. In addition, oxidized sterols may be formed. Thermal degra-... 

That the effect of BR is not simply due to the "oxidized" sterol structure is supported by our observation that oxysterols, which are strong inhibitors in mammalian cell cultures, were nearly inactive in our system. Again this points to... 

Analysis of the components of other fractions of simple lipids like free sterols, sterol esters, and wax esters by means of HPLC has some drawbacks, and it is usually performed using high-temperature GC. However, the most remarkable field of application of HPLC is the analysis of oxidized sterol and their esters, of biological interest, that used to be performed earlier using RP-LC with postcolumn fluorometric detection and is nowadays be carried out using LC coupled to MS, providing structural information on these complex derivatives. 

Dutta, P.C., Przybylski, R., Appelqvist, L-A. and Eskin, N.A.M. Formation and analysis of oxidized sterols in frying fats, in Deep Frying, pp. 112-150 (1996) (edited by E.G. Perkins and M.D. Erickson), American Oil Chemists Society Press, Champaign, IL. 

IDENTIFICATION OF THE COMPONENT REACTIONS OF OXIDATIVE STEROL C4-DEMETHYLATION... 

The path from squalene (114) to the corresponding oxide and thence to lanosterol [79-63-0] (126), C qH qO, cholesterol [57-88-5] (127), and cycloartenol [469-38-5] (128) (Fig. 6) has been demonstrated in nonphotosynthetic organisms. It has not yet been demonstrated that there is an obligatory path paralleling the one known for generation of plant sterols despite the obvious stmctural relationships of, for example, cycloartenol (128), C qH qO, to cyclobuxine-D (129), C25H42N2O. The latter, obtained from the leaves of Buxus sempervirens E., has apparentiy found use medicinally for many disorders, from skin and venereal diseases to treatment of malaria and tuberculosis. In addition to cyclobuxine-D [2241-90-9] (129) from the Buxaceae, steroidal alkaloids are also found in the Solanaceae, Apocynaceae, and LiUaceae. 

Since GAs as diterpenes share many intermediates in the biosynthetic steps leading to other terpenoids, eg, cytokinins, ABA, sterols, and carotenoids, inhibitors of the mevalonate (MVA) pathway of terpene synthesis also inhibit GA synthesis (57). Biosynthesis of GAs progresses in three stages, ie, formation of / Akaurene from MVA, oxidation of /-kaurene to GA 2" hyde, and further oxidation of the GA22-aldehyde to form the different GAs more than 70 different GAs have been identified. 

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

Bacterial removal of sterol side chains is carried out by a stepwise P-oxidation, whereas the degradation of the perhydrocyclopentanophenanthrene nucleus is prevented by metaboHc inhibitors (54), chemical modification of the nucleus (55), or the use of bacterial mutants (11,56). P-Sitosterol [83-46-5] (10), a plant sterol, has been used as a raw material for the preparation of 4-androstene-3,17-dione [63-05-8] (13) and related compounds using selected mutants of the P-sitosterol-degrading bacteria (57) (Fig. 2). 

Cholestanone has been prepared by the oxidation of dihydro-eholesterol with chromic anhydride in acetic acid solution.1 The yield is sometimes diminished as a result of the partial acetylation of the sterol. 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

CYP27A1 catalyzes the side chain oxidation (27-hydroxylation) in bile acid biosynthesis. Because bile acid synthesis is the only elimination pathway for cholesterol, mutations in the CYP27A1 gene lead to abnormal deposition of cholesterol and cholestanol in various tissues. This sterol storage disorder is known as cerebrotendinous xanthomatosis. CYP27B1 is the 1-alpha hydroxylase of vitamin D3 that converts it to the active vitamin form. The function of CYP27C1 is not yet known. 

PTLC was used to enrich the polar fraction of deep-fried potato chips and vegetable oils used in industrial frying operahons. After PTLC, capillary GC, GC-MS, and NMR were used to quantify sterols and sterol oxides in fried-potato products, as well as the composition of sterols in the oil used for frying [72]. 

Consumption of food with sterols and their oxides is a health concern. Oxidation products of phytosterol, including epimers of 7-ketositosterol and 7-hydroxycampes-terol, 7-ketocampesterol, epimers of 5,6-epoxy-sitosterol, 5,6-epoxycamposterol, 24 a-ethylcholestane-3(3,5,6 (3-triol, and 24 a-methylcholestane-3(3,5,6 (3-triol, in deep-fried potato chips in palm oil, sunflower oil, and high oleic sunflower oil were quanhtahvely analyzed by PTLC followed by GC and GC-MS [73]. 

Sea cucumbers (Holothuroidea, Echinodermata) appear to be unique in their mode of squalene oxide (37) cyclization. Tritium-labeled lanosterol (33), cycloartenol (32) and parkeol (38) were individually administered to the sea cucumber Holothuria arenicola. While the former two triterpenes were not metabolized [22], parkeol was efficiently transformed into 14x-methyl-5a-cho-lest-9(l l)-en-3/ -ol (39) (Scheme 3). Other A1 sterols present in H. arenicola were not found to be radioactive and were thus assumed to be of dietary origin. The intermediacy of parkeol was confirmed by the feeding of labeled mevalonate (23) and squalene (26) to the sea cucumber Stichopus californicus [15]. Both precursors were transformed into parkeol, but not lanosterol nor cycloartenol, aqd to 4,14a-dimethyl-5a-cholest-9(ll)-en-3/J-ol (40) and 14a-methyl-5a-cholest-9(ll)-en-3/ -ol. Thus, while all other eukaryotes produce either cycloartenol or lanosterol, parkeol is the intermediate between triterpenes and the 14-methyl sterols in sea cucumbers. 

Sterols are seldom detected in archaeological residues due to their low concentration and the tendency to undergo chemical degradation. In any case, the presence of sterols or of their oxidation products in a sample can help distinguish between animal and plant lipid materials cholesterol is the most abundant animal sterol, while campesterol and sitosterol are the two major plant ones. 

The differentiation of lipid media in samples from artworks on the basis of their sterol content has been attempted, but the tendency of sterols to oxidize means that they can rarely be detected in thin paint layers [56]. 

---