Bile acid synthesis from cholesterol: regulatory and auxiliary pathways

@article{Javitt1994BileAS,
  title={Bile acid synthesis from cholesterol: regulatory and auxiliary pathways},
  author={N. Javitt},
  journal={The FASEB Journal},
  year={1994},
  volume={8},
  pages={1308 - 1311}
}
  • N. Javitt
  • Published 1994
  • Chemistry, Medicine
  • The FASEB Journal
Bile acid synthesis from cholesterol can occur via two pathways, one initiated by sterol 27‐hydroxylase activity or one initiated by that of cholesterol 7α‐hydroxylase. In contrast to cholesterol 7α‐hydroxylase, which is found in the liver, sterol 27‐hydroxylase is a widely distributed mitochondrial enzyme with high activity in vascular endothelial cells. Although both pathways lead to the production of chenodeoxycholic and cholic acids, the key step, 7α‐hydroxylation, is governed by two… Expand
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References

SHOWING 1-10 OF 57 REFERENCES
Bile acid synthesis in humans: regulation of hepatic microsomal cholesterol 7 alpha-hydroxylase activity.
TLDR
It is concluded that the composition of individual bile acids may be more important than the total concentration of bile acid in the portal vein for the regulation of the cholesterol 7 alpha-hydroxylase activity in humans. Expand
Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis.
TLDR
The results suggest that bile acids and sterols are able to alter the transcription of the 7 alpha-hydroxylase gene and that this control explains the previously observed feedback regulation of bile acid synthesis. Expand
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.
TLDR
The structure of the sterol 26-hydroxylase cDNA reveals it to be a mitochondrial cytochrome P-450, and blotting experiments revealed that the mRNA for this enzyme is expressed in many tissues and that it is encoded by a low copy number gene in the rabbit genome. Expand
Cholesterol and bile acids regulate cholesterol 7 alpha-hydroxylase expression at the transcriptional level in culture and in transgenic mice.
TLDR
It is found that expression of an albumin enhancer-7 alpha-hydroxylase-lacZ fusion gene is restricted to the liver and is regulated by cholesterol and bile acids in a manner quantitatively similar to that of the endogenous gene. Expand
THE BIOLOGICAL CONVERSION OF CHOLESTEROL TO CHOLIC ACID
TLDR
It is thought that cholesterol labeled with deuterium should be of aid in throwing light on the relationship between cholesterol and bile acids; appearance of deuterio cholic acid after its administration would constitute clear evidence of direct conversion. Expand
Cholesterol is converted to 7 alpha-hydroxy-3-oxo-4-cholestenoic acid in liver mitochondria. Evidence for a mitochondrial sterol 7 alpha-hydroxylase.
TLDR
This study shows that the first reactions in the biosynthesis of bile acids can be exclusively mitochondrial and thereby bypass microsomal cholesterol 7 alpha-hydroxylase as the rate-limiting enzyme. Expand
Cholesterol and 27-hydroxycholesterol 7 alpha-hydroxylation: evidence for two different enzymes.
TLDR
The finding that Emulgen 913 selectively inactivates 7 alpha-hydroxylation of 27-hydroxycholesterol indicates that the metabolic pathway for bile acid synthesis from 27-Hydroxych cholesterol is not governed by cholesterol 7alpha-Hydroxylase. Expand
12 alpha-hydroxylase activity in human liver and its relation to cholesterol 7 alpha-hydroxylase activity.
TLDR
Results indicate that the increased ratio between the synthesis of cholic acid and chenodeoxycholic acid during cholestyramine treatment is due to a compensatory increase of the 12 alpha-hydroxylase activity. Expand
Sterol 27-hydroxylase: high levels of activity in vascular endothelium.
TLDR
The presence of the enzyme in endothelium provides a mechanism for preventing accumulation of intracellular cholesterol by initiating a pathway of bile acid synthesis different from that initiated by 7 alpha-hydroxylation of cholesterol in the liver. Expand
Effect of Biliary Drainage on Individual Reactions in the Conversion of Cholesterol to Taurocholic Acid
The effect of biliary drainage on incorporation of acetate into cholesterol and on four different enzyme systems in the metabolic pathway from cholesterol to taurocholic acid has been studied inExpand
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