Evidence for a Common Hepatic Cholesterol Precursor Site for Cholic and Chenodeoxycholic Acid Synthesis in Man

Cc, Schwartz; Vlahčevič, Z. Reno; Lg, Halloran; Nisman, Richard M.; Swell, Leon

doi:10.3181/00379727-156-39918

Cited by 8 publications

(3 citation statements)

References 7 publications

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“…Blood cell radioactivity was not measured. Chenodeoxycholic acid 3H and '4C specific activities are not shown in E.H.I or in the other subjects since they were virtually identical to cholic acid at all times as noted previously in bile fistula subjects ( 13).…”

Section: Resultsmentioning

confidence: 78%

Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate.

Schwartz¹,

Zech²,

VandenBroek³

et al. 1993

J. Clin. Invest.

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IntroductionOur aim was to identify and quantitate cholesterol pools and transport pathways in blood and liver. By studying bile fistula subjects, using several types of isotopic preparations, simultaneous labeling of separate cholesterol pools and sampling all components of blood and bile at frequent intervals, we developed a comprehensive multicompartmental model for cholesterol within the rapidly miscible pool. Data in six components (bile acids, esterified cholesterol in whole plasma, and free cholesterol in blood cells, bile, a lipoproteins, and ,B lipoproteins) were modeled simultaneously with the SAAM program. The analysis revealed extensive exchange of free cholesterol between HDL and liver, blood cells, and other tissues. There was net free cholesterol transport from HDL to the liver in most subjects. The major organ that removed esterified cholesterol from blood was the liver. A large portion (4,211 gmol) of total hepatic cholesterol comprised a pool that turned over rapidly (t1/2 of 72 min) by exchanging mainly with plasma HDL and was the major source of bile acids and biliary cholesterol. Only 6% of hepatic newly synthesized cholesterol was used directly for bile acid synthesis: the analysis showed that 94% of newly synthesized cholesterol was partitioned into the large hepatic pool (putative plasma membrane free cholesterol) which exchanged rapidly with plasma lipoproteins. Bile acid synthetic rate correlated directly with the size of the large hepatic pool.In conclusion, hepatic and blood cholesterol pools and transports have been quantitated. HDL plays a central role in free cholesterol exchange/transport between all tissues and plasma. In humans, the metabolically active pool comprises a large portion of total hepatic cholesterol that, in part, regulates bile acid synthesis. (J. Clin. Invest. 1993. 91:923-938.)

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Section: Resultsmentioning

confidence: 78%

Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate.

Schwartz¹,

Zech²,

VandenBroek³

et al. 1993

J. Clin. Invest.

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“…Some investigators using the tritiated water method (36), the [180,1 inhalation technique (21) or various cholesterol precursors (26,30,31,36) came to the same conclusion. In contrast to these findings, others (23)(24)(25) suggested a common cholesterol precursor pool for cholate and chenodeoxycholate in human beings and rats.…”

Section: Discussionmentioning

confidence: 51%

“…Earlier studies with various labeled precursors other than tritiated water or oxygen suggested that cholesterol and bile acids are derived from the same (23)(24)(25) or from separate (26)(27)(28)(29)(30)(31)(32) cholesterol pools in different species. However, using these older techniques, only differences in specific activities of secreted bile acids and biliary cholesterol were detectable, but the amount or proportion of bile acids synthesized from newly formed cholesterol could not be quantitated.…”

mentioning

confidence: 99%

Bile acid synthesis from newly synthesized vs. preformed cholesterol precursor pools in the rat

et al. 1993

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The present study defines the origin of cholesterol subserving bile acid synthesis in male rats with an extracorporal bile duct by labeling newly formed cholesterol with tritiated water. Within 6 hr after interruption of the enterohepatic circulation, the bile acid pool was depleted. At this early time point the proportion from de novo cholesterol was 8% and 12% for biliary cholesterol and cholate, but 18% and 19% for muricholate and chenodeoxycholate, respectively. This proportion gradually rose to 40%, 34%, 51% and 51%, respectively, at 15 to 30 hr. At 78 hr after bile diversion, 64% of cholate was labeled, compared with 84% to 88% of the other biliary lipids and 71% of plasma cholesterol. Total and labeled bile acid secretion exhibited the same diurnal rhythm. To allow differentiation between direct hepatocytic de novo synthesis of bile acids from acetate and recycling of labeled plasma cholesterol, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (pravastatin) was infused from 54 to 78 hr. It suppressed total synthesis of primary bile acids by 60% to 80% but decreased the tritium label of bile acids only from a range of 74% to 92% (54 hr) to a range of 54% to 63% (78 hr), which was in the range of plasma cholesterol (58%). We conclude that bile acids and biliary cholesterol are synthesized mostly from preformed (i.e., plasma) cholesterol, both immediately after depletion of the pool in enterohepatic circulation and after derepression. Moreover, the hepatic cholesterol pools subserving the synthesis of different bile acids and biliary cholesterol secretion are not identical.

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Molecular mechanisms controlling bile metabolism in health and disease

Carey¹

Falk Symposium

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Evidence for a Common Hepatic Cholesterol Precursor Site for Cholic and Chenodeoxycholic Acid Synthesis in Man

Cited by 8 publications

References 7 publications

Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate.

Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate.

Bile acid synthesis from newly synthesized vs. preformed cholesterol precursor pools in the rat

Molecular mechanisms controlling bile metabolism in health and disease

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