Estimation of Cholesterol and Bile Acid Turnover in Man by Kinetic Analysis

Quarfordt, Steven H.; Greenfield, Mary F.

doi:10.1172/jci107378

Cited by 38 publications

(12 citation statements)

References 27 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with the results recorded for the normolipidemic controls in the present study, the synthesis of CD has been found to be about half that of C (9,20). Similar results concerning the ratio between the synthetic rates of the two primary bile acids were reported recently by Quarfordt and Greenfield (21), who studied the metabolic fate of [1-1H]cholesterol.…”

Section: Discussionsupporting

confidence: 85%

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Einarsson¹,

Hellström²,

Kallner³

1974

J. Clin. Invest.

122

View full text Add to dashboard Cite

The total bile acid formation was within normal limits in patients with hyperlipoproteinemia types Ha and MIb. On the average the production of cholic acid (C) represented less than 50% of the total bile acid synthesis in both groups. The corresponding value recorded for the controls was 64±2% (mean±i-SEM). The synthesis of C in hyperlipoproteinemia type Ha was significantly below normal. Of the 27 patients with the type IV pattern, 18 had a synthesis of C and C + chenodeoxycholic acid (CD) that exceeded the upper range recorded for the controls. In these subjects the C formation represented 73±3% of the total bile acid synthesis. Similar findings were also encountered in the five patients with the type V lipoprotein pattern studied. The bile acid pool size of the 11 patients with hyperlipoproteinemia type IV, who had been cholecystectomized or suffered from cholelithiasis, was 900 mg smaller on the average than that of the other subjects with the same type of hyperlipoproteinemia. However, the pool size in the former subjects still tended to be higher than that of the control subjects without evidence of gallbladder "disease". In all groups of subjects the formation of bile acids tended to be higher in the male than in the female subjects. Bile acid synthesis showed no linear correlation to actual body weight, relative body weight, or body surface area. A moderate weight reduction in five patients (one with type IIb and four with type IV pattern) was followed by a 50% reduction of the C and CD synthesis.

show abstract

Section: Discussionsupporting

confidence: 85%

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Einarsson¹,

Hellström²,

Kallner³

1974

J. Clin. Invest.

122

View full text Add to dashboard Cite

show abstract

“…Note that some fraction of bile acid synthesis may take place via an alternate pathway in which sidechain oxidation begins with hydroxylation at carbon 25 (14,22). In that case, after oxidation of the hydroxyl group, the three-carbon fragment would be removed as acetone rather than propionic acid.…”

Section: Figurementioning

confidence: 99%

“…In animal models with an interrupted enterohepatic circulation given [4-"4C]cholesterol, this is not the case, since synthesized bile acid has a lower specific activity than serum cholesterol (24). However, in humans with an intact enterohepatic circulation, specific activity of bile acid has been virtually identical to specific activity of serum [4-'4C]cholesterol (25), indicating little or no preferential use of newly synthesized cholesterol for bile acid synthesis.…”

Section: Figurementioning

confidence: 99%

Regulation of bile acid synthesis in man. Presence of a diurnal rhythm.

Duane

Levitt²,

Mueller³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

“…The principal methods that have been used are the sterol balance technique, isotope dilution, and plasma cholesterol and squalene kinetics (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Much of our present concept of cholesterol metabolism within the plasma-liver compartment has come from studies of plasma cholesterol kinetics (4)(5)(6)(7)(8)(9)(10)(11)(12). It has been customary to administer labeled cholesterol to human subjects and follow the decay of the plasma cholesterol specific activity curves over periods from 1 to 12 mo.…”

Section: Introductionmentioning

confidence: 99%

“…The number of exponentials in this decay curve has been taken as the number of compartments with which plasma cholesterol interchanges. Recent studies (8)(9)(10) have defined three major body cholesterol compartments: a rapidly miscible pool (RMP),' a slowly miscible pool, and very slowly miscible pool. It has been suggested (9,10) that RMP comprises the cholesterol in the liver, plasma, RBC, and intestine.…”

Section: Introductionmentioning

confidence: 99%

Multicompartmental Analysis of Cholesterol Metabolism in Man

Schwartz¹,

Berman²,

Vlahčevič³

et al. 1978

J. Clin. Invest.

191

View full text Add to dashboard Cite

A B S T R A C T The present report has presented the first clear evidence in man for the existence of specific hepatic cholesterol precursor sites associated with the formation and secretion of bile acids and biliary cholesterol. These hepatic compartments derive virtually all their cholesterol from newly synthesized and lipoprotein free cholesterol. The model which is presented was formulated on current concepts of cholesterol metabolism in man and is concerned, at this initial stage, with the elucidation of the bile acid and biliary cholesterol compartments. The complexity of cholesterol metabolism in man necessitated an initial approach that would minimize the number of inputs of cholesterol into the system, allow for the sampling of several cholesterol compartments, and permit the simultaneous labeling of newly synthesized cholesterol and preformed cholesterol. To achieve these objectives, we studied the patient with a total bile fistula. Six patients were administered simultaneously pulse iinjections of labeled mevalonic acid and[14C]cholesterol. The qualitative features ofthe specific activity time course curves after labeled mevalonic acid revealed no precursor-product relationship between bile acid, biliary cholesterol, and plasma free cholesterol. The peak specific activity of the bile acids was reached in approximately 100 min and was higher than the biliary cholesterol, which was higher than the plasma free cholesterol. The plasma free cholesterol specific activity became higher than the other lipids after 12 h and remained higher throughout the period During the model development, the least number of compartments and transport pathways were introduced consistent with a good fit of the data. Of particular importance was the constraint that the model fit the data obtained from both [14C]cholesterol and labeled mevalonic acid. The same parameter values were used to fit the data from both tracers. The fluxes arrived at in the model indicate that 31% and 20%, respectively, of the cholesterol input into the bile acid and biliary cholesterol precursor sites were derived directly from the newly synthesized hepatic cholesterol. The remainder had its origin predominantly from lipoprotein free cholesterol. Plasma esterified cholesterol (as free) made a small contribution (11%) to the bile acid compartment. Similarly, 10% of the biliary cholesterol arose from an unknown hepatic site.The present report has provided the basis for a new procedure for studying in vivo cholesterol metabolism in man. Examination of the derived cholesterol flux rates between the compartments suggests the presence of an important mechanism regulating the partitioning of lipoprotein free cholesterol between the bile acid and biliary cholesterol precursor sites. Aberrations in the proportioning of precursor cholesterol between these sites could be a causative factor precipitating the excessive secretion of biliary cholesterol and the production of lithogenic bile.

show abstract

Estimation of Cholesterol and Bile Acid Turnover in Man by Kinetic Analysis

Abstract: A B S T R A C T The kinetics

Cited by 38 publications

References 27 publications

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia

Regulation of bile acid synthesis in man. Presence of a diurnal rhythm.

Multicompartmental Analysis of Cholesterol Metabolism in Man

Contact Info

Product

Resources

About