On the Formation of Deoxycholic Acid from Cholic Acid in the Rabbit. Bile Acids and Steroids 48.

Lindstedt, Sven; Sjövall, Jan; Harshbarger, F.; Magnéli, Arne; Pestmalis, Herbert; Åsbrink, Stig

doi:10.3891/acta.chem.scand.11-0421

Cited by 63 publications

(9 citation statements)

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“…As expected, only minute amounts of H3 were found in the bile acids from F.A. This agrees with the finding of Bergstrom and Lindstedt and their associates that 7-a-hydroxylation is an integral part of bile acid biosynthesis and that the formation of deoxycholic acid is due to subsequent bacterial action on cholic acid in the intestinal lumen (19,20). The minute amounts of H3 (less than 15 per cent of the C14 cpm per ,umole) observed in the bile acid samples might reflect some slight isotopic nonhomogeneity in the labeling of the 7-a-H3-cholesterol used.…”

Section: Resultssupporting

confidence: 79%

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

Goodman¹,

Avigan²,

Wilson³

1962

J. Clin. Invest.

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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...

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Section: Resultssupporting

confidence: 79%

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

Goodman¹,

Avigan²,

Wilson³

1962

J. Clin. Invest.

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“…Washout curves for bile salt secretion after acute bile fistulation, similar to those described in this study, have also been noted in rabbits (47) and in man (48). Eriksson (26) first suggested that the rise in bile salt secretion which follows the low point of the washout curve was due to increased bile salt synthesis by the liver.…”

Section: Resultssupporting

confidence: 66%

Effects of controlled interruption of the enterohepatic circulation of bile salts by biliary diversion and by ileal resection on bile salt secretion, synthesis, and pool size in the rhesus monkey

Dowling¹,

Mack²,

Small³

1970

J. Clin. Invest.

239

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ABSTRA CT The effects of controlled interruption of the enterohepatic circulation (EHC) of bile salts by biliary diversion on bile volume, bile salt secretion and synthesis rates, bile salt pool size, and the relationship to fecal fat excretion were studied in 16 rhesus monkeys.Bile from a chronic bile fistula was returned to the intestine through an electronic stream-splitter which, by diverting different percentages of bile to a collecting system, provided graded and controlled interruption of the EHC.The increase in hepatic bile salt synthesis in response to interruption of the EHC was limited and reached a maximum rate at 20% interruption of the EHC. Up to this level of biliary diversion, the increased hepatic synthesis compensated for bile salt loss so that bile salt secretion and pool size were maintained at normal levels. With diversion of 33% or more, there was no further increase in hepatic bile salt synthesis to compensate for external loss, and as a result there was diminished bile salt secretion, a reduction in bile salt pool size, and steatorrhea was observed.

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“…They are not interconvertible (Bergstrom, Danielsson & Samuelsson, 1960). Deoxycholate (DC), which normally accounts for 15-30% of the total, is produced by bacterial removal of the 7a-hydroxy1 group of cholate (Lindstedt, 1957a;Ekdahl & Sjovall, 1958) and is therefore termed a secondary bile salt.…”

Section: Introductionmentioning

confidence: 99%

The Selective Inhibition of Chenodeoxycholate Synthesis by Cholate Metabolites in Man

Pomare

Low-Beer

1975

Clinical Science

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1. Seven normal volunteers took 0-28--0-42 mmol (100--150 mg) of deoxycholate by mouth. This resulted in a reduced proportion of chenodeoxycholate in bile and an increased proportion of deoxycholate. Cholate was unchanged. 2. Cholate and chenodeoxycholate pools and rats of synthesis were determined in four of the subjects by simultaneously labelling each pool with 14C-labelled bile acids. The chenodeoxycholate pool and rate of synthesis decreased after deoxycholate administration. Cholate synthesis and pool size did not change appreciably. 3. The proportion of deoxycholate in bile samples of sixty-two subjects with intact enterohepatic circulation was found to be inversely related to the proportion of chenodeoxycholate in bile, but not to the cholate. 4. It is suggested that inhibition of chenodeoxycholate synthesis by deoxycholate, the principal bacterial product of cholate, regulates the size of the chenodeoxycholate pool independently of the total amount of bile salt.

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On the Formation of Deoxycholic Acid from Cholic Acid in the Rabbit. Bile Acids and Steroids 48.

Cited by 63 publications

References 0 publications

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

The Metabolism of Desmosterol in Human Subjects During Triparanol Administration*

Effects of controlled interruption of the enterohepatic circulation of bile salts by biliary diversion and by ileal resection on bile salt secretion, synthesis, and pool size in the rhesus monkey

The Selective Inhibition of Chenodeoxycholate Synthesis by Cholate Metabolites in Man

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