The effect of portacaval transposition on hepatic cholesterol‐7α‐hydroxylase activity in the rat

Boyd, George S.; Lawson, Margaret E.

doi:10.1016/0014-5793(76)80344-4

Cited by 10 publications

(2 citation statements)

References 18 publications

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“…The serum cholesterol lowering effect of a portacaval anastomosis might be due to one of the following mechanisms: (1) decreased hepatic or extrahepatic cholesterol synthesis; (2) changes in lipoprotein composition or metabolism; (3) alteration of cholesterol absorption or reabsorption, (4) modified pool sizes; and ( 5 ) increased cholesterol catabolism to form bile acids or elevated biliary cholesterol excretion. Cholesterol-7u-hydroxylase, the rate limiting enzyme of cholesterol catabolism to bile acids, has been found to have an increased activity per g liver weight after creation of a portacaval anastomosis in rats [8,9] . On the other hand, due t o the marked liver weight reduction in shunted animals there is only a slightly increased total enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

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Effect of portacaval shunt on biliary cholesterol and bile salt secretion in normal rats

Bützow¹,

Dammann²,

Czok

1978

Eur J Clin Investigation

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In order to assess the role of bile secretion in the serum cholestrol lowering effect of a portacaval anastomosis in rats, bile flow rate, bile salt and cholesterol secretion in bile were determined. The study comprised five groups of animals: (1) rats with protacaval shunt cholesterol free food ad libitum. (2) sham-operated and pair-fed controls; (3) unoperated, pair-fed controls; (4) unoperated controls on cholesterol free diet ad libitum; and (5) unoperated controls on normal laboratory rat chow ad libitum. Bile flow rate showed no difference in any of the groups on cholesterol free diet. Bile salt secretion was significantly elevated in shunted animals (87.1 +/- 7.0 nmol/min) as compared with pair-fed sham-operated (64.7 +/- 20.0 nmol/min) and unoperated controls (56.0 +/- 22.3 nmol/min). Biliary cholesterol output tended to be higher in shunted animals but this was not statistically significant. The data indicate that the atrophied rat liver in shunted animals is able to maintain a normal bile flow and to increase bile salt secretion. Thus, the serum cholesterol lowering action of a portocaval anastomosis may be partly due to an increased cholesterol catabolism to bile salts.

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Section: Discussionmentioning

confidence: 99%

“…On the basis of the presented data, no definitive interpretation is possible. The possibility of an enhanced cholesterol degradation might be supported by the increased cholesterol-7a-hydroxylase activity in shunted rats [8,9]. Furthennore, the preferred substrate for bile acid formation is newly synthesized cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Effect of portacaval shunt on biliary cholesterol and bile salt secretion in normal rats

Bützow¹,

Dammann²,

Czok

1978

Eur J Clin Investigation

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Hepatocyte ultrastructure in rats with portacaval shunt

et al. 1982

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The principal reported morphological consequence of portacaval shunt in the rat is liver atrophy. The present study was designed to investigate ultrastructural changes in hepatocytes using electron microscopy morphometry. Two weeks following portacaval shunt, rat livers were fixed by perfusion and hepatocyte organelles from the two opposite zones of the acinus (zones 1 and 3) were quantified. Liver weight/body weight decreased by 50%, hepatocyte-specific volume decreased by 30% (28% in zone 1 nd 35% in zone 3). Estimated sinusoidal space increased, and estimated number of hepatocytes decreased by 50%. Hepatocytes had a normal ultrastructure except for mitochondria. Smooth endoplasmic reticulum-specific surface area was reduced by 65% (zone 3), and rough endoplasmic reticulum surface density was increased in zone 1 only. Mitochondria-specific volume was unchanged but decreased inner and outer membrane-specific surface area in zone 3 suggests in this zone a change in their conformation and possibly their number. Golgi-rich area surface density increased but not significantly. Hepatocyte loss and atrophy and rearrangement of organelles represent a new ultrastructural steady state following portacaval shunt that may help explain the new functional steady state.

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Biosynthesis of bile acids in mammalian liver

Kevrešan

Kuhajda

Kandrac

et al. 2006

Eur. J. Drug Metab. Pharmacokinet.

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The biosynthesis of bile acids in mammalian liver and its regulation, together with the physiological role of bile acids, are reviewed in this article. Bile acids are biosynthesized from cholesterol in hepatocytes. Several steps are involved including epimerisation of the 3beta-hydroxyl group, reduction of the delta4 double bond to the 5beta-H structural arrangement, introduction of alpha-hydroxyl groups at C7 or C7 and C12 and, finally, oxidative degradation of the side chain by three carbon atoms. This gives the primary bile acids, cholic and chenodeoxycholic acids. Cholesterol-7alpha-hydroxylation is the rate determining step in the biosynthesis of cholic and chenodeoxycholic acids. Feedback regulation of cholesterol biosynthesis occurs by various mechanisms including termination of the synthesis of specific cytochromes P-450, modulation of specific cytosol proteins, short-term changes in the process of phosphorylation-dephosphorylation and changes in the capacity of the cholesterol pool as a substrate. Prior to being exported from the liver, bile acids are conjugated with glycine and taurine to produce the bile salts. After excretion into the intestinal tract, primary bile acids are partly converted to secondary bile acids, deoxycholic and lithocholic acids, by intestinal microorganisms. The majority of bile acids is absorbed from the intestinal tract and returned to the liver via the portal blood, so that only a small fraction is excreted in the feces. Bile acids returned to the liver can be reconjugated and reexcreted into the bile in the process of enterohepatic recycling. In addition to the physiological function of emulsifying lipids in the intestinal tract, bile acids are particularly important in respect of their ability to dissolve and transport cholesterol in the bile.

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The effect of portacaval transposition on hepatic cholesterol‐7α‐hydroxylase activity in the rat

Cited by 10 publications

References 18 publications

Effect of portacaval shunt on biliary cholesterol and bile salt secretion in normal rats

Effect of portacaval shunt on biliary cholesterol and bile salt secretion in normal rats

Hepatocyte ultrastructure in rats with portacaval shunt

Biosynthesis of bile acids in mammalian liver

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