Effect of cellulose in the diet on the recovery of dietary plant sterols from the feces.
(65/103)
In one normal subject, J.S., fed several formula diets in a sterol balance study, only 25-58% of the ingested plant sterols were recovered from the stool. The dietary plant sterols were completely recovered from the stools of five other men. Plant sterol recovery was complete in all men when a diet of mixed general foods was consumed. Since the chief differences in composition of the formula and the diet of mixed general foods were related to the different contents of cellulose and lactose, these components were added to the formula diet of J.S., and plant sterol balance studies were then carried out. The addition of fresh celery or pulverized cellulose to the formula diet partially corrected the usual fecal loss of plant sterols (80% being recovered). Lactose in the formula was only slightly corrective. However, the addition of both cellulose and lactose led to complete recovery of the ingested plant sterols in the feces. Bacterial cultures of stools were incubated with added cholesterol-4-(14)C, and a linear relationship between losses of sterol during balance studies and in vitro incubations was observed; that is, a considerable loss of the labeled cholesterol from cultures after the formula diet, but not after the diet of mixed general foods. This in vitro loss was also corrected by the addition of cellulose and lactose to the formula diet. The loss of the sterol nucleus in the intestinal tract may occur at times because of the lack of certain dietary constituents. It is hypothesized that the metabolism of intestinal tract bacteria is altered when certain constituents are not present in the diet, and that these bacteria may then degrade the sterol nucleus. (+info)
Isolation and identification of new constituents in milk fat.
(66/103)
After removal of cholesterol on a digitonin column, the unsaponifiable matter of milk fat was examined for alcoholic substituents. Derivatization with pyruvic acid chloride 2,6-dinitrophenylhydrazone and fractionation of the derivatives gave four main fractions. The second, the hexane-benzene fraction, was shown by thin-layer chromatography to have a mobility similar to many common sterols. The hexane-benzene fraction was saponified and gave rise to free alcohols, which were then analyzed on a combination gas-liquid chromatograph-mass spectrometer. Dihydrolanosterol, previously unreported in milk fat, and lanosterol, previously identified but never confirmed, were characterized. The sterols which were precipitated on the digitonin column, were removed, and by the use of the combination gas-liquid chromatograph-mass spectrometer beta-sitosterol was identified. In addition, lanosterol and dihydrolanosterol were isolated from the unsaponifiable matter by chromatography on Florisil. (+info)
Sterol synthesis in the human arterial intima.
(67/103)
Intimal sterol synthesis was examined in isolated human arterial segments obtained at surgery or at postmortem examination. The tissues were incubated with acetate-1-(14)C and mevalonate-2-(14)C and the incorporation of these precursors into sterols was determined. Intimal sterols were isolated by multiple chromatographic techniques and purified by bromination and oxidation procedures. The results indicate that the arterial intima can incorporate acetate and mevalonate into cholesterol, cholestanol, and squalene. Cholestanol was the major sterol synthesized by the arterial wall, but cholesterol production was also consistently observed. The findings suggest that local synthesis is a potential source of sterol accumulation within the arterial wall. The conversion of cholesterol to other sterols was also studied in terminally ill patients receiving labeled cholesterol before death. Tissue analyses revealed the presence of labeled cholestanol as well as cholesterol in the tissue 5-104 days after labeled cholesterol administration. The results demonstrate the conversion of cholesterol to cholestanol in man and suggest that the exchange of cholestanol between the blood and tissues is similar to that of cholesterol. (+info)
Nuclear magnetic resonance and infrared spectra of delta-24- and C-24 saturated steroids.
(68/103)
The infrared (IR) and nuclear magnetic resonance (NMR) spectra of eight Delta(24)-steroids and nine C-24 saturated steroids were examined. NMR spectra allow unambiguous assignment of the biologically important Delta(24)-bond; introduction of a Delta(24)-bond causes the appearance of peaks at Delta 1.60 and 1.68 associated with the C-26, C-27 isopropylidene methyls, while C-24 saturated steroids of the cholestane series possess peaks at Delta 0.82 and 0.91 associated with the C-26, C-27 gem-dimethyls. IR spectra show a good correlation between the introduction of a Delta(24)-bond and a marked decrease in intensity of a band at 1365 cm(-1). NMR and IR spectra also allow an inference about the presence and location of nuclear double bonds in Ring B of cholesterol precursors. (+info)
Conversion of 7-alpha,12-alpha-dihydroxycholest-4-en-3-one to 5-alpha-cholestane-3-alpha, 7-alpha,12-alpha-triol by iguana liver microsomes.
(69/103)
The role of 7alpha,12alpha-dihydroxycholest-4-en-3-one as an intermediate in the formation of 5alpha-bile acids from cholesterol was investigated with liver preparations of Iguana iguana in vitro. The microsomal fraction of iguana liver catalyzed the transformation of 7alpha,12alpha-dihydroxycholest-4-en-3-one to 5alpha-cholestane-3alpha,7alpha,12alpha-triol in good yield. 7alpha,12alpha-dihydroxy-5alpha-cholestan-3-one served as an intermediate. Under the conditions employed, formation of the corresponding 5beta-isomers could not be detected. High speed supernatant solution and mitochondrial fraction of iguana liver did not reduce 7alpha,12alpha-dihydroxycholest-4-en-3-one to a measurable extent. The microsomal enzyme system required NADPH as hydrogen donor and was inactive in the presence of NADH. It is suggested that 7alpha,12alpha-dihydroxycholest-4-en-3-one may serve as a common intermediate in the formation of 5alpha- and 5beta-bile acids from cholesterol. (+info)
Experimental cholelithiasis in the rabbit induced by cholestanol feeding: effect of neomycin treatment on bile composition and gallstone formation.
(70/103)
Fed cholestanol is converted by the rabbit to 5alpha-bile acids which coprecipitate with the normally occurring 5beta-bile acids to form gallstones composed of calcium and sodium glycoallodeoxycholate and glycodeoxycholate. The present study shows that oral administration of large doses of neomycin prevents gallstone formation in the cholestanol-fed rabbit and reduces the elevated concentration of allodeoxycholic acid in bile, with a reciprocal increase in allocholic acid concentration. The reduction in the concentration of allodeoxycholic acid and in the incidence of gallstones is proportional to the dose of neomycin; at a concentration of allodeoxycholic acid below about 20% of total bile acids, gallstone formation does not occur. Neomycin probably exerts its action by modifying the anerobic intestinal flora which dehydroxylate allocholic acid to allodeoxycholic acid; if so, this suggests that both hepatic and bacterial transformations are essential steps in the pathogenesis of cholestanol-induced cholelithiasis. The bile of rabbits on a normal diet contains allodeoxycholic acid (5% of total bile acids). A similar decrease in allodeoxycholic acid concentration and reciprocal increase in allocholic acid concentration is observed when neomycin is administered to rabbits on a normal diet. (+info)
7-alpha-hydroxylation of cholestanol by rat liver microsomes.
(71/103)
In a study of the mechanism whereby 5alpha-bile acids are formed from cholestanol, the 7alpha-hydroxylation of cholestanol was investigated in rat liver preparations in vitro. It was found that in the presence of NADPH and oxygen, rat liver microsomes catalyzed the 7alpha-hydroxylation of cholestanol to the same extent as that of cholesterol. The rate of the hydroxylation was enhanced by prior treatment of the experimental rats with cholestyramine (a bile acid sequestrant) or by establishment of bile fistulas-i.e., by partial or complete removal of bile acids from the enterohepatic circulation. The 7-hydroxylation reaction was further stimulated by pretreatment of the animals with phenobarbital, a drug known to produce increased biosynthesis of hepatic endoplasmic membranes. The 7alpha-hydroxylase was inhibited by the reaction product, by sterols with 7-keto or 7beta-hydroxyl groups, and also by mono- and dihydroxy bile acids of the 5beta-series, although cholic acid or taurocholate produced no inhibition unless added in high concentrations. The results of these studies are in accord with the concept that the presence of a Delta(5)-double bond is not required for the enzymatic formation of the 7alpha-hydroxy derivative. The rate of this hydroxylation reaction in vitro appears to depend on the concentration of bile salts in the enterohepatic circulation of the experimental animals from whom the microsomes were obtained. (+info)
Comparative studies of bile salts. Bile salts of sturgeons (Acipenseridae) and of the paddlefish Polyodon spathula: a new partial synthesis of 5 beta-cyprinol.
(72/103)
1. Bile salts of the sturgeons Acipenser guldenstaedti Brandt, Acipenser stellatus Pall and Huso huso L. and of the paddlefish Polyodon spathula Walbaum are shown to be closely similar, consisting mainly of taurocholate with minor amounts of tauroallocholate and the monosulphates of bile alcohols. The bile alcohols, comprising less than 10% of the bile salts, are mixtures with high proportions of substances resembling C(27) tetrols and of C(27) pentols, including 5beta-cyprinol and (probably) 5alpha-cyprinol. 2. 5beta-Cyprinol (3alpha,7alpha,12alpha,26,27-pentahydroxy-5beta-cholestane) was made from cholic acid via 3alpha,7alpha,12alpha-triacetoxy-5beta-cholan-24-ol in an overall yield of about 0.8%. 3. The chemical nature of chondrostean bile salts agrees with the systematic position of the fishes and suggests further correspondence between evolution at the morphological and molecular levels. (+info)