Metabolism of 3β-hydroxycholest-5-en-26-oic acid in hamsters

Ayaki, Yoshikazu; Kok, Engeline; Javitt, Norman B.

doi:10.1007/bf01951761

Cited by 7 publications

(13 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An alternative explanation for changes in the relative proportions of cholic acid and chenodeoxycholic or ,-muricholic acids can be the existence of another pathway in the formation of bile acids, in addition to the major pathway involving initial 7a-hydroxylation of cholesterol [10,30], as has been suggested by several investigators to occur in the rat, hamster, rabbit and man [11][12][13][14][15]31]. This route may involve initial 26-hydroxylation of cholesterol by mitochondria, leading predominantly to the formation of chenodeoxycholic acid and /3-muricholic acid [11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis

Princen¹,

Meijer

Wolthers

et al. 1991

Biochemical Journal

102

View full text Add to dashboard Cite

Bile acid synthesis, determined by conversion of [4-14C]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52 % (rat) and 45 % (human) inhibition at 10/,M. The decreased bile acid production in rat hepatocytes was due only to a fall in the synthesis of,-muricholic and chenodeoxycholic acids (-64 % at 10 4M-cyclosporin A), with no change in the formation of cholic acid. In isolated rat liver mitochondria, 26-hydroxylation of cholesterol was potently inhibited by the drug (concn. giving half-maximal inhibition = 4/tM). These results suggest that cyclosporin A blocks the alternative pathway in bile acid synthesis, which leads preferentially to the formation of chenodeoxycholic acid.

show abstract

Section: Discussionmentioning

confidence: 99%

Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis

Princen¹,

Meijer

Wolthers

et al. 1991

Biochemical Journal

102

View full text Add to dashboard Cite

show abstract

“…Administration of 27-hydroxycholesterol to rats, hamsters, rabbits and humans results in the formation of 7α-hydroxylated products [36][37][38]. Sterol 27-hydroxylase catalyzes the 27-hydroxylation of cholesterol, the first step in the acidic pathway [39] (Fig.…”

Section: Acidic or Alternative Pathwaymentioning

confidence: 99%

Enzymes in the Conversion of Cholesterol into Bile Acids

Norlin¹,

Wikvall

2007

CMM

168

137

View full text Add to dashboard Cite

This article aims to give an overview on the characterization, properties and regulation of enzymes, particularly the cytochrome (CYP) P450 enzymes, in the formation of bile acids from cholesterol. Bile acids are biologically active molecules that promote absorption of dietary lipids in the intestine and stimulate biliary excretion of cholesterol. Bile acids and oxysterols, formed from cholesterol, act as ligands to nuclear receptors regulating the expression of important genes in cholesterol homeostasis. Thus, the bioactivation of cholesterol into bile acids is crucial for regulation of cholesterol homeostasis. The primary human bile acids, cholic acid and chenodeoxycholic acid, are formed from cholesterol via several pathways involving many different enzymes. Many of these enzymes are cytochrome P450 (CYP) enzymes, introducing a hydroxyl group in the molecule. The "classic" pathway of bile acid formation starts with a 7alpha-hydroxylation of cholesterol by CYP7A1 in the liver. The "acidic" pathway starts with a hepatic or extrahepatic 27-hydroxylation by CYP27A1. There also exist some quantitatively minor pathways which may be of importance under certain conditions. Formation of cholic acid requires insertion of a 12alpha-hydroxyl group performed by CYP8B1. Oxysterols are precursors to bile acids, participate in cholesterol transport and are known to affect the expression of several genes in cholesterol homeostasis. Enzymes with capacity to form and metabolize oxysterols are present in liver and extrahepatic tissues. The enzymes, nuclear receptors and transcription factors involved in bile acid biosynthesis are potential pharmaceutical targets for the development of new drugs to control hypercholesterolemia and to prevent atherosclerosis and other diseases related to disturbed cholesterol homeostasis. The review will also discuss some inborn errors of bile acid biosynthesis and the recently acquired knowledge on the genetic defects underlying these diseases.

show abstract

“…The inability of low inundations of 27-OH-C to interfere with LDL uptake and degradation could be explained by the observation that oxysterols can be metabolized by 7o-hydroxylase to form bile acids [22,29]. It can be speculated that 7a-hydroxylase maintains the expression of LDL receptors by metabolizing (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Several groups have suggested 27-hy droxycholesterol to be a likely candidate [l&22, 26,27]. 27-Hydroxycholesterol is synthesized from cholesterol by a cytochrome PhsO containing mitochondrial enzyme (C27-steroid 27-hydroxyla~) in most tissues [22,26,28], represents an intermediate in the synthesis of bile acids [22,29], is normally present in human plasma lipoprotein [22,30] and in healthy and athero~lero~~ human aorta [31,32]. Recently, Saucier et al [24], although not con&rmed by others [33], reported the presence of increased levels of oxysterols (24-, 25-and 27-hydroxycholesterol) and repression of HMG-CoA reductase in cholesterol fed-mice according to the hypothesis that intracellular oxysterols regulate the level of the reductase.…”

mentioning

confidence: 99%

27‐Hydroxycholesterol modulation of low density lipoprotein metabolism in cultured human hepatic and extrahepatic cells

et al. 1993

View full text Add to dashboard Cite

-Hydr~xych~~~tero~*~, 25-hy~oxycholesterol and choiesterol suppressed LDL uptake and degradation in human extrahepatic and hepatic cell lines in a concentrationdependent manner. Cholesterol was the least potent, and the inhibitory et&ct of oxysterols was more pronounced in skin fibroblasts and in endothelial cell line EAhy 926 than in hepatoma HepG2 cells. Shorter incubations were required for oxysterols to achieve 50% inhibition of LDL uptake and degradation in all cultured cells. The inhibition of LDL catabolism in extrahepatic cells by 27.hydroxycholesterol occurred at concentrations close to those observed in human plasma (0.2-0.6 PM). The results support a possible role of 27-hydroxycholesterol, a physiological oxysterol, in the regulation of cellular cholesterol homeostasis in non-hepatic tissues.

show abstract

Metabolism of 3β-hydroxycholest-5-en-26-oic acid in hamsters

Cited by 7 publications

References 12 publications

Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis

Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis

Enzymes in the Conversion of Cholesterol into Bile Acids

27‐Hydroxycholesterol modulation of low density lipoprotein metabolism in cultured human hepatic and extrahepatic cells

Contact Info

Product

Resources

About