The Relation of Plasma and Biliary Cholesterol to Bile Acid Synthesis in Man *

Rosenfeld, Robert; Hellman, Louis M.

doi:10.1172/jci103908

Cited by 29 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus it is known that the liver free cholesterol pool is in rapid isotopic equilibrium with serum free cholesterol, and that the bile acids derived from the former are in rapid isotopic equilibrium with both (23). Furthermore, in the studies with Patient F.A.…”

Section: Discussionmentioning

confidence: 99%

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

Goodman¹,

Avigan²,

Wilson³

1962

J. Clin. Invest.

View full text Add to dashboard Cite

Recent studies with triparanol (1-[p-,3-diethylaminoethoxyphenyl ]-1-(p-tolyl) -2-(p-chlorophenyl)ethanol) have demonstrated that this compound inhibits cholesterol biosynthesis by blocking the reduction of 24-dehydrocholesterol (desmosterol) to cholesterol (2-4). Administration of triparanol to laboratory animals and to man results in the accumulation of desmosterol in the plasma and tissues, usually with some concomitant lowering of the plasma total sterol concentration (2, 5). In studies with human subjects it was observed that after about 2 weeks the desmosterol concentration tended to plateau at an average level of 27 per cent of the total circulating sterols (5). The ratios of desmosterol to cholesterol in animal tissues (2) differed somewhat from the ratios in plasma. In addition, injection of the cholesterol precursor 2-C14-mevalonic acid during triparanol administration resulted in the rapid appearance of labeled desmosterol in blood, while no significant radioactivity appeared in cholesterol in the first few days (5).The object of the present experiments was to study the metabolism of desmosterol in patients receiving triparanol. Since cholesterol serves as the biosynthetic precursor for several physiologically important compounds, including bile acids and steroid hormones, the question arose whether desmosterol could also function as a precursor for these compounds without first being transformed into cholesterol. The studies reported herein demonstrate the direct conversion of desmosterol to both bile acids and to steroid hormones, and also provide information about the over-all metabolism of this sterol in the triparanol-treated man. EXPERIMENTALClinical material. Both of the patients studied were hospitalized on a metabolic ward of the Clinical Center.* Presented in part at the First International Pharmacology Meeting, Stockholm, Sweden, August, 1961 (1).Patient G.B. was a 55 year old man with known arteriosclerotic heart disease and mild hypercholesterolemia; since 1957 he had maintained a satisfactory and stable cardiac status. At the time of the present study he had been taking 250 mg triparanol daily for 4 weeks, and had a total serum sterol level in the high normal range. Patient F.A. was a 40 year old man with a 4-to 5-year history of gout and essential hyperlipemia. At the time of this study he had been on an isocaloric low purine diet for several weeks, and both the gout and hyperlipemia were in remission. He received 250 mg triparanol daily for 2 weeks prior to the start of this study.Design of study. Each study was begun in the fasting patient by the rapid injection of 20 /Ac of 2-C14-mevalonic acid, in isotonic saline, into an antecubital vein. Patient F.A. also received, in the same injection, 20 jsc of 7-a H'-cholesterol, previously incorporated into his own serum lipoproteins by the method of Avigan (6). Blood samples were collected 3 hours later from the opposite antecubital vein, and at varying intervals thereafter. We obtained bile in the early mornings by duodenal intubation, em...

show abstract

Section: Discussionmentioning

confidence: 99%

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

Goodman¹,

Avigan²,

Wilson³

1962

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…If more than one experiment 809 was performed on a patient the tubing was allowed to proceed and thle same procedure was repeated on subsequent days at a lower level of the intestitie. Any interference with recirculated cholesterol was not of importance as absorbed cholesterol is highly diluted with the cholesterol pool of the organism (Rosenfeld and Hellman) (6).…”

Section: Experimental Designmentioning

confidence: 99%

Studies on Intestinal Cholesterol Absorption in the Human

Borgström¹

1960

J. Clin. Invest.

127

View full text Add to dashboard Cite

“…Previous studies on the turnover of cholesterol in human plasma have treated plasma cholesterol ester as a single homogeneous entity (15)(16)(17). Since plasma cholesterol ester exists as a mixture * Submitted for publication April 2, 1964; accepted July 2, 1964. Supported by research grants AM-05986 and HE-05741 from the National Institutes of Health.…”

mentioning

confidence: 99%

The In Vivo Turnover of Individual Cholesterol Esters in Human Plasma Lipoproteins *

Goodman¹

1964

J. Clin. Invest.

View full text Add to dashboard Cite

It has long been known that plasma cholesterol consists largely of a mixture of several different fatty acid esters of cholesterol. This was first indicated in 1896, when Hiirthle isolated cholesteryl palmitate, oleate, and stearate from an alcoholic extract of serum (1). Subsequent early studies on the ratio of free to ester cholesterol in plasma demonstrated that most of the plasma cholesterol normally exists in ester form (2). More recent studies, using gas-liquid chromatography for the analysis of the cholesterol ester fatty acids, have defined the composition of the plasma cholesterol esters in a variety of species (3-8).In addition, plasma cholesterol normally is distributed among several different plasma lipoprotein fractions. Most of the plasma cholesterol of man is typically present in the low density, beta-lipoprotein fraction, with smaller amounts present in the high density and the very low density lipoproteins (9-12). These lipoproteins show small but consistent differences in their ratio of free to ester cholesterol (11,13). Recent analyses of the cholesterol ester composition of each human plasma lipoprotein have demonstrated strong similarities in the cholesterol ester composition of the different lipoproteins (13). Small but statistically significant differences do, however, exist between the different lipoproteins. Larger differences between lipoprotein cholesterol ester patterns have been reported by Lindgren and Nichols (14).Previous studies on the turnover of cholesterol in human plasma have treated plasma cholesterol ester as a single homogeneous entity (15-17). Since plasma cholesterol ester exists as a mixture * Submitted for publication April 2, 1964; accepted July 2, 1964. Supported by research grants AM-05986 and HE-05741 from the National Institutes of Health. MethodsForty-four microcuries of DL-2-C'4-mevalonic acid, in solution in isotonic saline, was injected intravenously into each of two fasting normal men. The C'4-mevalonic acid 1 was prepared for injection as described earlier (18). The subjects, a 39-year-old Negro (subject WB) and an 18-year-old Caucasian (subject EH), ate their usual diets except for a slight reduction in fat intake for one week preceding, and during, the period of the study. Serial blood samples were collected in syringes moistened with a solution of heparin, and plasma samples were collected and processed as described in detail elsewhere (13). In brief, small samples of plasma were extracted immediately, and larger volumes of plasma were used for the serial separation of lipoproteins as discussed by Havel, Eder, and Bragdon (10

show abstract

The Relation of Plasma and Biliary Cholesterol to Bile Acid Synthesis in Man *

Cited by 29 publications

References 17 publications

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

Studies on Intestinal Cholesterol Absorption in the Human

The In Vivo Turnover of Individual Cholesterol Esters in Human Plasma Lipoproteins *

Contact Info

Product

Resources

About