Metabolism of Cholest-5-ene-3β, 26-diol in the Rat and Hamster

Wachtel, Nili; Emerman, Sidney; Javitt, Norman B.

doi:10.1016/s0021-9258(18)92011-9

Cited by 73 publications

(8 citation statements)

References 16 publications

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“…The melting point of the isolated diol (173-175°C) was comparable with those reported for aortal cholest-5-ene-3fl,26-diol (172.5-174°C and 174.5-176.5°C;van Lier & Smith, 1969) and for the (25R)sterol derived from kryptogenin [177-1780C, Scheer et al (1956173-175°C, Danielsson (1961); 175.5-176.50C, Wachtel et al (1968)]. The melting point of the diol diacetate (121-123°C), however, was considerably lower than that of the (25R) isomer (128-1290C) [literature m.p.…”

Section: Resultssupporting

confidence: 80%

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The isolation of cholest-5-ene-3β,26-diol from human brain

Smith

Gilbert

Harland

et al. 1974

Biochemical Journal

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Section: Resultssupporting

confidence: 80%

“…The melting point of the diol diacetate (121-123°C), however, was considerably lower than that of the (25R) isomer (128-1290C) [literature m.p. : 128-129°C, Scheer et al (1956), Wachtel et al (1968; 130-1310C,…”

Section: Resultsmentioning

confidence: 99%

The isolation of cholest-5-ene-3β,26-diol from human brain

Smith

Gilbert

Harland

et al. 1974

Biochemical Journal

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“…Since we have shown elsewhere that rat liver mitochondria convert 3fhydroxychol-5-enoic acid into lithocholic acid, chenodeoxycholic acid and f-muricholic acid (Mitropoulos & Myant, 1967b), it is reasonable to suppose that these acids are also formed via 26hydroxycholesterol by liver mitochondria. This would explain the observation of Wachtel et al (1968) that 26-hydroxy[3H]cholesterol is converted into radioactive 3,B-hydroxychol-5-enoic acid, chenodeoxycholic acid and muricholic acid in bile-fistulated rats. The finding that in the absence of exogenous 26-hydroxycholesterol the specific radioactivity of 26-hydroxycholesterol was higher than that of 3,hydroxychol-5-enoic acid would be expected if 26hydroxycholesterol is an intermediate in the formation of this acid.…”

Section: Discussionmentioning

confidence: 86%

The formation of cholest-5-ene-3β,26-diol as an intermediate in the conversion of cholesterol into bile acids by liver mitochondria

Mitropoulos

Avery

Myant

et al. 1972

Biochemical Journal

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1. When [(14)C]cholesterol was incubated with rat liver mitochondria, radioactive 26-hydroxycholesterol, 3beta-hydroxychol-5-enoic acid and other bile acids were isolated from the incubation mixture. 2. In the absence of added 26-hydroxycholesterol, the specific radioactivity of the 26-hydroxycholesterol formed from [(14)C]cholesterol during the incubation was higher than that of the 3beta-hydroxychol-5-enoic acid. Addition of increasing amounts of 26-hydroxycholesterol led to a progressive fall in the specific radioactivity, and to a progressive increase in the mass, of the 3beta-hydroxychol-5-enoic acid recovered at the end of the incubation. 3. It is concluded that 26-hydroxycholesterol is an intermediate in the formation of 3beta-hydroxychol-5-enoic acid from cholesterol. 4. Comparison of the specific radioactivity of the 26-hydroxycholesterol formed in the incubation mixture with that of the added [(14)C]cholesterol indicates that endogenous cholesterol in mitochondria is accessible to cholesterol 26-hydroxylase.

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“…Using the same approach to the synthesis of 25R,26hydroxycholesterol as Scheer, Thompson, and Mosettig, Sidney Emerman, and I prepared a radioactive compound of much higher specific activity (14) and found that in the rat it was metabolized to both chenodeoxycholic and cholic acid, although the latter was present in much smaller amounts.…”

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confidence: 99%

25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles

Javitt

2002

Journal of Lipid Research

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The CYP27 gene is expressed in arterial endothelium, macrophages, and other tissues. The gene product generates sterol intermediates that function as ligands for nuclear receptors prior to their transport to the liver for metabolism, mostly to bile acids. Most attention has been given to 27-hydroxycholesterol as a ligand for LXR activated receptors and to chenodeoxycholic acid as a ligand for farnesoid X activated receptors (FXRs). Expression of the pathway in macrophages is essential for normal reverse cholesterol transport. Thus, ABC transporter activity is upregulated, which enhances cholesterol efflux. Absence of these mechanisms probably accounts for the accelerated atherosclerosis that occurs in cerebrotendinous xanthomatosis. Accumulation of 27-hydroxycholesterol in human atheroma is puzzling and may reflect low levels of oxysterol 7 ␣hydroxylase activity in human macrophages. The same enzyme determines the proportion of mono-, di-, and trihydroxy bile acids synthesized in the liver. Oxysterol 7 ␣hydroxylase deficiency is a molecular basis for cholestatic liver disease. Chenodeoxycholic acid, the major normal end product, downregulates expression of cholesterol 7 ␣ -hydroxylase via the FXR/short heterodimer protein nuclear receptor and thus limits total bile acid production.The challenge is to quantify in a physiologic setting the magnitude of the pathway in different tissues and to further evaluate the biologic roles of all the intermediates that may function as ligands for orphan nuclear receptors or via other regulatory mechanisms. -Javitt, N. B. 25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles.

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Metabolism of Cholest-5-ene-3β, 26-diol in the Rat and Hamster

Cited by 73 publications

References 16 publications

The isolation of cholest-5-ene-3β,26-diol from human brain

The isolation of cholest-5-ene-3β,26-diol from human brain

The formation of cholest-5-ene-3β,26-diol as an intermediate in the conversion of cholesterol into bile acids by liver mitochondria

25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles

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