The measurement of sulphated and non-sulphated bile acids in serum using gas-liquid chromatography

Campbell, C. B.; McGuffie, Christine; Powell, Lawrie W.

doi:10.1016/0009-8981(75)90045-5

Cited by 45 publications

(10 citation statements)

References 22 publications

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“…Interindividual differences in the serum LCA levels in humans are reported (Campbell et al, 1975;Cowen et al, 1977). Moreover, it is reported that average serum concentrations of total bile acids in healthy subjects and hepatitis patients are 5.3 (1.1-16.4) and 44.9 (2.7-80.3) M, respectively, and that LCA accounts for 13% (0 -32%) and 18% (0 -53%) of the total bile acid in healthy subjects and in hepatitis patients, respectively (Campbell et al, 1975). Because LCA undergoes enterohepatic circulation, its concentration in intestines could be high enough to activate VDR.…”

Section: Discussionmentioning

confidence: 99%

Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction in Vitro and in Vivo

Matsubara¹,

Yoshinari²,

Aoyama³

et al. 2008

Drug Metab Dispos

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ABSTRACT:Lipophilic bile acids are suggested to be involved in the endogenous expression of CYP3A4 in human and experimental animals as ligands of nuclear receptors. To verify the nuclear receptor specificity, the bile acid-mediated induction of CYP3A4 has been studied in vitro and in vivo in the present study. Lithocholic acid (LCA) strongly enhanced the activities of the CYP3A4 reporter gene, which contained multiple nuclear receptor binding elements, in both HepG2 and LS174T cells. The introduction of small interfering RNA for human vitamin D receptor (VDR), but not for human pregnane X receptor, reduced the LCA-induced activation of the reporter gene in these cells, suggesting the major role of VDR in the LCA induction of CYP3A4. Consistently, oral administration of LCA (100 mg/kg/day for 3 days) increased Cyp3a protein levels in the intestine but not in the liver, where a negligible level of VDR mRNA is detected. The selective role of VDR was tested in mice with the adenoviral overexpression of the receptor. Oral administration of LCA had no clear influence on the CYP3A4 reporter activity in the liver of control mice. In mice with the adenovirally expressed VDR, LCA treatment (100 or 400 mg/kg/day for 3 days) resulted in the enhanced reporter activities and increased levels of Cyp3a proteins in the liver. These results indicate the selective involvement of VDR, but not pregnane X receptor, in the LCA-mediated induction of both human and mouse CYP3As in vivo.

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Section: Discussionmentioning

confidence: 99%

Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction in Vitro and in Vivo

Matsubara¹,

Yoshinari²,

Aoyama³

et al. 2008

Drug Metab Dispos

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“…Since bile salt is required for enzyme activation, it has long been thought that this enzyme has minimal activity outside the digestive tract where bile salt concentration is low. However, it must be noted that fasting serum bile salt concentration is approximately 10 M and increases by 3-fold postprandially (120,121). Bile acid concentrations are also typically 6-fold higher in portal blood than in peripheral circulation and may reach as high as 100 M (122).…”

Section: Lipoprotein Metabolism and Atherosclerosismentioning

confidence: 99%

Carboxyl ester lipase

Hui

Howles

2002

Journal of Lipid Research

186

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Carboxyl ester lipase (CEL), previously named cholesterol esterase or bile salt-stimulated (or dependent) lipase, is a lipolytic enzyme capable of hydrolyzing cholesteryl esters, tri-, di-, and mono-acylglycerols, phospholipids, lysophospholipids, and ceramide. The active site catalytic triad of serine-histidine-aspartate is centrally located within the enzyme structure and is partially covered by a surface loop. The carboxyl terminus of the protein regulates enzymatic activity by forming hydrogen bonds with the surface loop to partially shield the active site. Bile salt binding to the loop domain frees the active site for accessibility by water-insoluble substrates. CEL is synthesized primarily in the pancreas and lactating mammary gland, but the enzyme is also expressed in liver, macrophages, and in the vessel wall. In the gastrointestinal tract, CEL serves as a compensatory protein to other lipolytic enzymes for complete digestion and absorption of lipid nutrients. Importantly, CEL also participates in chylomicron assembly and secretion, in a mechanism mediated through its ceramide hydrolytic activity. Cell culture studies suggest a role for CEL in lipoprotein metabolism and oxidized LDL-induced atherosclerosis. Thus, this enzyme, which has a wide substrate reactivity and diffuse anatomic distribution, may have multiple functions in lipid and lipoprotein metabolism, and atherosclerosis. Carboxyl ester lipase (CEL), previously named pancreatic cholesterol esterase and also known as bile salt-stimulated (or -dependent) lipase, is a nonspecific lipolytic enzyme capable of hydrolyzing cholesteryl esters, tri-, di-, and mono-acylglycerols, phospholipids, lysophospholipids, and ceramide (1-3). The hydrolysis of water-insoluble carboxyl esters with long chain fatty acyl groups by CEL requires its activation by bile salt. However, CEL hydrolysis of water-soluble substrates such as carboxyl esters with short chain fatty acids or lysophospholipids does not have an absolute dependence on bile salt activation. The CEL protein is synthesized primarily in the pancreatic acinar cells and lactating mammary glands of higher mammals. Small amounts of CEL are found in other tissues, particularly the liver, macrophages, endothelial cells, and eosinophils (4-10). Extensive research has been performed in recent years on the structure-function relationship of this protein as well as its physiological role in lipid metabolism. A significant body of work has also been devoted to studying CEL processing and transport in pancreatic acinar cells. The latter topic was reviewed recently (11) and will be discussed only briefly in this article when appropriate. This article will present an updated review on the structure-function studies of CEL as well as an in-depth discussion on the current understanding of its role in lipid metabolism. PROTEIN STRUCTURE-FUNCTION RELATIONSHIP Active siteThe nucleotide sequence of CEL from various species shows that it is a highly conserved protein belonging to the ␣ / ␤ hydrolase family. The carb...

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“…In plasma, the concentration of bile acid is ∼ 10 μM (42) and in postprandial portal plasma is ∼ 10-fold greater (43). The concentration of bile salts in this range is well in excess of the nanomolar levels shown to affect the conformation of CEL (44).…”

Section: Discussionmentioning

confidence: 99%

Plasma carboxyl ester lipase activity modulates apolipoprotein B–containing lipoprotein metabolism in a transgenic mouse model

Weng

Harrison

et al. 2008

Metabolism

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Pancreatic carboxyl ester lipase (CEL) is in the plasma of many mammals, including humans and rats, but not mice. In vitro, CEL hydrolyzes cholesterol esters (CE) of apoB-containing lipoproteins (apoB-Lp). To study the effect of CEL on metabolism of apoB-Lp and atherosclerosis in vivo, apoEknockout (EKO) mice, which have high plasma levels of apoB-Lp and are prone to atherosclerosis, were made to secrete CEL into plasma by introducing a transgene containing a liver-specific promoter and rat CEL cDNA. Plasma CEL activity in EKO-CEL mice was comparable to that found in rats. Evidence of modification of apoB-Lp by plasma CEL in vivo was an increase in the free cholesterol:CE ratio of apoB-Lp from mice on chow or a Western-type diet. In addition, plasma total cholesterol levels were elevated in EKO-CEL mice, with the elevation found exclusively in the apoBLp fraction. Associated with the increase in steady-state apoB-Lp levels was an increase in the plasma half life of very low density lipoproteins (VLDL) in EKO-CEL mice, measured by the clearance rate of injected VLDL. Interestingly, in spite of the increase of apoB-lipoproteins, the atherosclerotic lesion did not differ between EKO and EKO-CEL mice on a Western-type diet. In summary, our results demonstrate that plasma CEL modulates apoB-Lp metabolism in vivo, resulting in reduced VLDL clearance and elevated plasma cholesterol levels.

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The measurement of sulphated and non-sulphated bile acids in serum using gas-liquid chromatography

Cited by 45 publications

References 22 publications

Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction in Vitro and in Vivo

Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction in Vitro and in Vivo

Carboxyl ester lipase

Plasma carboxyl ester lipase activity modulates apolipoprotein B–containing lipoprotein metabolism in a transgenic mouse model

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