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PubMed1992

Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit.

Feedback regulation of derepressed hepatic bile acid biosynthesis was studied individually with glycocholic, glycodeoxycholic, and glycoursocholic acids by infusion into bile acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile acid pool (90% glycodeoxycholic acid, 10% glycocholic acid) within 24 hours and elicited maximal bile acid synthesis after about 72 hours, at which time glycocholic acid became the only biliary bile acid (greater than 98%). Replacement of the bile acid pool with glycocholic acid or glycodeoxycholic acid at a rate equivalent to the hepatic endogenous bile acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic acid, the 7 beta-hydroxy epimer of glycocholic acid, failed to suppress synthesis. Hepatic bile acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7 alpha-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic acid. Glycodeoxycholic acid infusion depressed cholesterol 7 alpha-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic acid infusion, were not affected by glycodeoxycholic acid infusion, but increased 19% and 43%, respectively, during glycoursocholic acid infusion. These results show that in rabbits the feedback regulation of hepatic bile acid synthesis depends on the hepatic flux of the normally present endogenous bile acids glycocholic acid and glycodeoxycholic acid but does not respond to the 7 beta-hydroxy glycoursocholic acid. Glycocholic acid inhibits both HMG-CoA reductase and cholesterol 7 alpha-hydroxylase while glycodeoxycholic acid affects primarily cholesterol 7 alpha-hydroxylase. Thus, the regulation of bile acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile acid synthesis.

Animals↗

PubMed1993

Different feedback regulation of hepatic cholesterol and bile acid synthesis by glycodeoxycholic acid in rabbits.

BACKGROUND: To explore the sexual difference in the feedback regulation of hepatic bile acid synthesis, glycodeoxycholic acid (GDCA) was administered to 15 male and 14 female rabbits. METHODS: After bile diversion, GDCA equivalent to the hepatic bile acid influx was infused intraduodenally. Biliary cholic acid output represented bile acid synthesis. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase activities and steady state messenger RNA (mRNA) levels were determined. RESULTS: GDCA inhibited bile acid synthesis less in female than in male rabbits. Hepatic HMG-CoA reductase activity decreased 39% in males, but increased 48% in females. Hepatic cholesterol 7 alpha-hydroxylase activity decreased similarly in males and females, and mRNA levels decreased 86% in males but were unchanged in females. CONCLUSIONS: (1) Total bile diversion stimulated both hepatic cholesterol and bile acid synthesis by activating the rate-controlling enzymes and increasing mRNA levels. (2) GDCA decreased mRNA levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in males, but mRNA levels did not decrease in females. (3) Bile acid synthesis was sustained in females because continued biosynthesis of cholesterol provided a substrate for cholesterol 7 alpha-hydroxylase and stimulus for enzyme formation.

Animals↗

PubMed1999

[Glycodeoxycholic acid changes the membrane fluidity and superoxides of lipids in hepatocytes].

OBJECTIVES: To explore the mechanisms of hepatocyte injury caused by glycodeoxycholic acid (GDCA) through studies on the roles of GDCA to membrane fluidity and superoxides of lipids of hepatocyte. METHODS: GDCA was used to treat hepatocytes of rat cultured in vitro and changes in cell membrane fluidity and malondialdehyde(MDA) were observed. RESULTS: In the presence of GDCA (final concentration of 250 mumol/L), the concentration of hepatocyte MDA of GDCA increased significantly (P < 0.001) and membrane fluidity decreased (P < 0.02) after culture of 1 or 4 hours. ALT was directly related to MDA and fluorescence polarization (P), r was 0.945 and 0.986, respectively. CONCLUSION: GDCA can induce the increase of MDA and decrease of fluidity of hepatocyte membrane, and finally cause hepatocyte injury.

Animals↗

PubMed2000

Characterization of partition and thermodynamic properties of cephalosporins using micellar electrokinetic chromatography in glycodeoxycholic acid solution.

Micellar electrokinetic chromatography (MEKC) was introduced to evaluate the hydrophobicity of cephalosporins (cefpim, cefpirom, cefazolin, ceftazidim, cephradin, cefuroxim, cefotaxim, cephapirin and cephalothin). Partition coefficients of cephalosporins were calculated between a micelle and an aqueous phases from the measurement of the migration time, provided the critical micelle concentration and the phase ratio are known. Thermodynamic quantities such as enthalpy and entropy changes of micellar solubilization were calculated from the temperature dependence on the partition coefficients. Sodium glycodeoxycholate in low-salt aqueous solutions was employed to prepare a micellar solution. Substances for pharmaceutical purposes have to meet several requirements to be well-tolerated. Therefore, they are often derived from naturally occurring ones, e.g., from the bile salts in bile juice. The electrophoretic velocity of a micelle and the phase ratio between the micelle of the glycodeoxycholic acid and the aqueous phase were calculated. Partial specific volumes at different temperatures (from 20 to 45 degrees C) were measured using dynamic light scattering. The logarithm of the partition coefficients and the migration factor in the micellar system were correlated with the logarithm of the 1-octanol-water partition coefficients.

Cephalosporins↗

PubMed2006

Single-step analysis of individual conjugated bile acids in human bile using 1H NMR spectroscopy.

1H and 13C NMR spectra of intact human bile were assigned using one-dimensional (1H and 13C) and two-dimensional (1H-1H and 1H-13C) experiments. Individual conjugated bile acids--glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid--were identified. The bile acids were quantified accurately and individually in a single step by using distinct and characteristic amide signals. Making use of 13C NMR, the study also suggests a way to analyze unconjugated bile acids separately, if present. Chemical shift assignments and rapid single-step analysis of individual conjugated bile acids from intact bile presented herein may have immense utility in the study of bile acid metabolism and deeper understanding of hepatobiliary diseases.

Bile↗

PubMed2005

Micellar electrokinetic chromatography of bilirubin, related compounds, and selected drugs with mixtures of binary bile salts.

Micellar electrokinetic chromatography was used to study the behavior of quinine, propranolol, bilirubin, biliverdin dimethyl ester, and xanthobilirubin methyl ester in single and binary bile salt micelle systems comprised of glycocholic acid and glycodeoxycholic acid. Micelle systems studied had total bile salt concentrations in the range of 10-33 mM with molar ratios of 1:0, 2:1, 1:1, 1:2, and 0:1 glycocholic acid:glycodeoxycholic acid. A pH 8.5 phosphate-borate buffer system was used. For all analytes except bilirubin, the smallest migration factors were found in glycocholic acid solutions and the largest in glycodeoxycholic acid solutions. Intermediate migration factors were found for all compounds except bilirubin in the binary bile salt systems. Bilirubin behaved uniquely with its largest migration factors in the binary bile salt mixtures.

Bile Acids and Salts↗

PubMed2005

1H and 13C NMR characterization and stereochemical assignments of bile acids in aqueous media.

The unconjugated bile acids cholic acid, deoxycholic acid, and chenodeoxycholic acid; their glycine and taurine conjugates glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid; and a taurine conjugated ursodeoxycholic acid, tauroursodeoxycholic acid, were characterized through 1H and 13C NMR in aqueous media under the physiological pH region (7.4 +/- 0.1). Assignments of 1H and 13C signals of all the bile acids were made using a combination of several one- and two-dimensional, homonuclear (1H-1H) and heteronuclear (1H-13C) correlations as well as spectral editing NMR methods. Stereochemical assignment of the five-membered ring of the bile acids is reported here for the first time. The complete characterization of various bile acids in aqueous media presented here may have implications in the study of the pathophysiology of biliary diseases through human biliary fluids using NMR spectroscopy.

Bile Acids and Salts↗

PubMed1997

Effect of bile acids and estradiol on thymidine incorporation into DNA in MCF-7 and MCF-10A breast cell lines.

Bile acid conjugates are found in human breast cyst fluid in average concentrations about 50-fold greater than those in blood. Because epidemiologic studies have linked colon and breast cancer and aberrant bile acid profiles are associated with colon cancer risk, we decided to study the influence of bile acid conjugates (glycochenodeoxycholic acid, glycodeoxycholic acid, glycocholic acid, and glycolithocholic acid) on thymidine incorporation into DNA in cancer (MCF-7) and noncancer (MCF-10A) human mammary cell lines. The two lines responded differently. In MCF-7, bile acids, except for glycolithocholic acid, stimulated thymidine incorporation. Estradiol caused even greater stimulation, an effect that was not influenced further by the addition of bile acids. Bile acids suppressed incorporation in MCF-10A cells. Estradiol at 1 nM had no effect, but 10 nM estradiol was stimulatory. In most cases bile acids appeared to diminish the incorporations observed with estradiol alone, but not significantly. The relevance of these studies to the possible impact of bile acids on the course of fibrocystic disease of the breast would require further investigation.

Bile Acids and Salts↗

PubMed2026

Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis.

Alterations in circulating bile acids (BAs) have been reported in inflammatory bowel disease (IBD), but the consistency of these changes across clinically relevant comparisons remains unclear. Our goal was to investigate systemic BA alterations in IBD using a metabolomics meta-analysis with an exploratory analysis of BA-related gene expression as a supporting context. A systematic review and meta-analysis of 28 metabolomics studies examined blood BA profiles associated with IBD, IBD diagnosis, and disease activity assessment. Univariate analysis and logistic regression modeling of two independent IBD cohorts explored the blood BA-related genes and IBD. Across 28 studies that comprised 5056 IBD patients, 1721 healthy controls, and 314 non-IBD patients, 131 BAs were reported. Eight predefined clinical comparisons were eligible for the meta-analysis. Lower secondary BA levels were consistently observed in IBD patients compared with controls, between UC and CD, and in active versus remission patients. Deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid were frequently decreased, whereas glycocholic acid was increased in certain comparisons. Transcriptomics analyses revealed differential expression of several BA-related genes in blood, including SLC51A, ABCB4, and ACOT8, across the comparisons. Our findings identify consistent circulating BA alterations in IBD and highlight the relevance of blood BA for future biomarker research in the diagnosis and disease activity assessment.

Humans↗

PubMed2004

Microencapsulated Genetically Engineered Lactobacillus plantarum 80 (pCBH1) for Bile Acid Deconjugation and Its Implication in Lowering Cholesterol.

Cholesterol is known to be a major risk factor for coronary heart disease (CHD). Current treatments for elevated blood cholesterol include dietary management, regular exercise, and drug therapy with fibrates, bile acid sequestrants, and statins. Such therapies, however, are often suboptimal and carry a risk for serious side effects. This study shows that microencapsulated Lactobacillus plantarum 80 (pCBH1) cells can efficiently break down and remove bile acids, and establishes a basis for their use in lowering blood serum cholesterol. Results show that microencapsulated LP80 (pCBH1) is able to effectively break down the conjugated bile acids glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) with bile salt hydrolase (BSH) activities of 0.19 and 0.08 $\mu$ mol DCA/mg CDW/h respectively. This article also summarizes the physiological interrelationship between bile acids and cholesterol and predicts the oral doses of microencapsulated Lactobacillus plantarum 80 (pCBH1) cells required for lowering cholesterol.

Journal Article↗

PubMed1987

Aspects of the effect of bile salts on Candida albicans.

Cholic acid, chenodeoxycholic acid, deoxycholic acid, glycocholic acid, glycodeoxycholic acid, hyodeoxycholic acid and lithocholic acid as their sodium salts, were fungistatic to the growth of Candida albicans. Of the compounds tested, cholic acid, deoxycholic acid and chenodeoxycholic acid were the most active. In combination with other antifungal agents only cholic acid exhibited synergism with amphotericin B, whilst the imidazole antifungal agents inhibited the action of the bile salts. The bile salt minimal inhibitory concentrations were close to the critical micelle concentrations. Even though the compounds are surface active they did not cause loss of intracellular K+ and were without effect on oxygen consumption. The bile salts, particularly cholic acid, produced morphological changes that gave rise to swollen cells.

Amphotericin B↗

PubMed1995

Mechanism of ketoconazole-induced elevation of individual serum bile acids in the rat: relationship to the effect of ketoconazole on bile acid uptake by isolated hepatocytes.

Ketoconazole, an imidazole derivative, has been implicated in a number of hepatic dysfunctions. The aim of the present study was to determine the effect of in vivo treatment of rats with ketoconazole on individual serum bile acid levels and the in vitro effects of ketoconazole on the hepatocellular uptake of two bile acids and two other model substrates transported by liver cells. Male Sprague-Dawley rats were treated i.p. with a single injection of ketoconazole of 25 mg/kg (n = 4) or 50 mg/kg (n = 4); the control group (n = 4) received the vehicle only at a dose of 1 ml/kg. Blood samples were collected at 4 hr after dosing. With high-performance liquid chromatography, the serum was assayed for individual serum bile acids. At the higher dose, ketoconazole produced a significant increase in serum levels of cholic acid, taurocholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid and taurochenodeoxycholic acid compared with the control group (P < .05). Cholic acid, taurocholic acid and chenodeoxycholic acid levels were significantly raised in rats treated with the lower dose. In vitro, ketoconazole strongly inhibited the hepatocellular uptake of [14C]cholic acid, [14C]taurocholic acid and [3H]ouabain but not [14C]2-aminoisobutyric acid, which indicated that the effect is relatively specific. The kinetics of inhibition were competitive and the inhibition constants for taurocholate and ouabain were 6 and 1 microM, respectively. Ketoconazole inhibited by both Na(+)-dependent taurocholate uptake and stimulated bile acid countertransport of preloaded hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Toxicity order of cholanic acids using an immobilised cell biosensor.

There is considerable published evidence of the use of cells of various species to evaluate the toxicity of numerous compounds, many of pharmaceutical interest. The coupling of cell colonies with a suitable transduction device has led to the development in recent years of toxicity biosensors based on the alteration of a process or a cell metabolic function by the toxic substance under examination. A biosensor based on immobilised yeast cells (Saccharomyces cerevisiae) has been developed recently in this department for the purpose of performing a rapid toxicity test in aqueous environmental matrices. This biosensor has now been used in the toxicity screening of a number of sodium salts of conjugated and free cholanic acids. The "toxicity degree" scale, which was found by placing in decreasing order the values of the slopes of the straight lines obtained by quantifying changes in the behaviour of the respirometric curve, plotted before and after incubation, using known concentrations of cholanic acid sodium salts, was: deoxycholic acid > chenodeoxycholic acid > ursodeoxycholic acid > cholic acid, for free cholanic acids; and glycodeoxycholic acid > glycochenodeoxycholic acid > glycocholic acid, for glycocholanic acids. These values are in good agreement with published toxicity data obtained in vitro. This sensor can thus be considered to provide a valid instrument for the preliminary evaluation of the toxicity of organic compounds or drugs.

Biosensing Techniques↗

PubMed1996

Increasing hepatic cholesterol 7alpha-hydroxylase reduces plasma cholesterol concentrations in normocholesterolemic and hypercholesterolemic rabbits.

The effect of bile acid depletion and replacement with glycodeoxycholic acid on plasma cholesterol concentrations, hepatic low-density lipoprotein (LDL) receptor binding and messenger RNA (mRNA) levels, and hepatic activities and mRNA levels for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7alpha-hydroxylase was investigated in 19 New Zealand white (NZW) and 15 Watanabe heritable hyperlipidemic (WHHL) rabbits. Bile acid depletion was produced by external bile drainage for 5 days, which maximized cholic acid synthesis. Replacement was achieved by infusing glycodeoxycholic acid intraduodenally for 24 hours so that the hepatic bile acid flux reached prefistula levels. Plasma and liver cholesterol concentrations were 13 times and 50% greater, respectively, hepatic LDL receptor-mediated binding was 26% less, and cholesterol 7alpha-hydroxylase activity and mRNA levels were 62% and 86% less in WHHL than NZW rabbits. After bile drainage, plasma cholesterol concentrations decreased 29% in NZW rabbits and 40% in WHHL rabbits and were associated with a 2.1-fold increase in hepatic LDL receptor-mediated binding in the NZW rabbits, but there was no change in the WHHL rabbits. Cholesterol 7alpha-hydroxylase activity and mRNA levels increased three and four times in NZW and WHHL rabbits, respectively, although liver cholesterol levels remained unchanged. Replacement with exogenous glycodeoxycholic acid increased plasma cholesterol concentrations 1.7 times in NZW rabbits and decreased enhanced cholesterol 7alpha-hydroxylase activity 54%, mRNA levels 86%, cholic acid synthesis 38%, and hepatic LDL receptor-mediated binding 57% in NZW rabbits. Bile acid depletion stimulated cholic acid synthesis by up-regulating cholesterol 7alpha-hydroxylase to use cholesterol and reduce plasma concentrations substantially in both NZW and WHHL rabbits, although LDL receptors did not function in WHHL rabbits. Glycodeoxycholic acid replacement inhibited elevated cholesterol 7alpha-hydroxylase, cholic acid synthesis, and hepatic LDL receptor binding to reestablish baseline plasma cholesterol levels in NZW rabbits. Hypercholesterolemia in WHHL rabbits was related to the combination of dysfunctional LDL receptors and inhibited cholesterol 7alpha-hydroxylase. Plasma cholesterol concentrations were reduced significantly when cholesterol 7alpha-hydroxylase was stimulated even in the absence of LDL receptor function.

Animals↗

PubMed1983

Serum concentration of bile acids in guinea pigs as an indicator of liver damage caused by aflatoxins.

Serum concentrations of glycocholic acid (GA) and glycodeoxycholic acid (GDA) and serum activity of aspartate aminotransferase (AST) were determined after guinea pigs had been fed 0, 0.005, 0.010, 0.015, 0.020, or 0.030 mg of aflatoxin B1 equivalents daily for 21 days. Mean serum concentrations for the 20 control guinea pigs were GA, 3.70 mumole/L; GDA, 0.12 mumole/L; and AST, 59.7 IU. Concentrations of GA and GDA in treated guinea pigs were significantly higher than those in controls (P less than 0.05) at doses of aflatoxin greater than or equal to 0.010 mg/day. The highest serum concentrations of bile acids were in guinea pigs given the higher doses of aflatoxin. Activities of AST in treated guinea pigs were significantly higher than those in controls for only 2 dosage levels (0.010 and 0.030 mg/day). Bile acids in the serum of guinea pigs was a more sensitive indicator of liver damage caused by aflatoxin than was AST.

Aflatoxins↗

PubMed1986

Naturally occurring conjugated bile acids, measured by high-performance liquid chromatography, in human, dog, and rabbit bile.

The aim of this study was to determine the biliary pattern of conjugated bile acids after stimulation of their enterohepatic circulation. Conjugated bile acids were separated by reversed-phase ion-pair chromatography without prior derivatization. A MicroPak SP-C18-IP-4 column was used as non-polar matrix, and an ionic alkyl compound, tetrabutylammonium phosphate, was added to the mobile phase, which was a mixture of acetonitrile and water. Quantification was made by UV absorption at 210 nm with external standardization. In fourteen human patients with external biliary drainage after papillotomy there was preferential glycine conjugation. The mean values were 36.5% for glycocholic acid, 33% for glycochenodeoxycholic acid, and 10.0% for glycodeoxycholic acid. Only 15.2% of the biliary bile acids were taurine metabolites. Conjugates of ursodeoxycholic acid were below 2.1%. In most cases, conjugated lithocholic acid was not detected. Within 4 h after ingestion of a standardized meal there were no significant changes in the biliary bile acid pattern. In four dogs (beagles), glycine-conjugated bile acids were lacking. The mean values were 74.3% for taurocholic acid, 14.9% for taurodeoxycholic acid, and 5.3% for taurochenodeoxycholic acid. In six rabbits, 87.4% of biliary bile acids was identified as glycodeoxycholic acid and 5.3% as glycocholic acid. In conscious dogs, as well as in rabbits, the stimulation of biliary secretion by cholecystokinin and/or secretin had no effect on the biliary bile acid spectrum. Evidently, there is a difference in the biliary composition of conjugated bile acids between humans, dogs, and rabbits. Because of the different physicochemical behaviour of glycine- and taurine-conjugated bile salts, it seems difficult to compare the therapeutic effect of gallstone dissolution in various species.

Animals↗

PubMed2005

Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin-sensitive mechanism in murine and human hepatocytes.

Several studies have argued that G-protein-coupled receptors (GPCR) have the capacity to promote activation of receptor tyrosine kinases. The current studies were performed to examine the regulation of the extracellular regulated kinase (ERK)1/2 and AKT pathways by conjugated and unconjugated bile acids in primary hepatocytes. Deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), taurochenodeoxycholic acid (TCDCA), glycochenodeoxycholic acid (GCDCA), taurocholic acid (TCA), glycocholic acid (GCA), and tauroursodeoxycholic acid (TUDCA) all activated ERK1/2 in primary rat hepatocytes that was abolished by inhibition of ERBB1, and significantly reduced by ROS quenching agents. Bile acid-induced AKT activation was blunted by preventing ERBB1 activation and ROS generation. Treatment of rat hepatocytes with pertussis toxin (PTX) did not alter ERK1/2 and AKT activation induced by DCA or CDCA but abolished pathway activations by conjugated bile acids. Similar data to those with PTX were obtained when a dominant negative form of G(i1alpha) was overexpressed. Treatment of rat hepatocytes with TDCA and TCA promoted guanosine triphosphate (GTP) loading of G(i1alpha), G(i2alpha), and G(i3alpha) in vitro. Treatment of rat hepatocytes with PTX abolished TDCA-induced tyrosine phosphorylation of ERBB1. Similar findings to those in rat hepatocytes were also obtained in primary mouse and human hepatocytes, but not in established rodent or human hepatoma cell lines. In conclusion, collectively our findings demonstrate that unconjugated bile acids activate hepatocyte receptor tyrosine kinases and intracellular signaling pathways in a ROS-dependent manner. In contrast, conjugated bile acids primarily activate receptor tyrosine kinases and intracellular signaling pathways in a GPCR (G(ialpha))-dependent and ROS-dependent manner.

Animals↗

PubMed1985

Human beta-glucuronidase. Studies on the effects of pH and bile acids in regard to its role in the pathogenesis of cholelithiasis.

Human bile contains a considerable amount of endogenous beta-glucuronidase. The effects of pH and bile acids on its activity have been studied in regard to its role in the pathogenesis of cholelithiasis. beta-Glucuronidase, purified from human liver to homogeneity, was structurally stable between pH 4 and 10, but was active only over a much narrower range of pH, with a pH optimum of 5.2. The inactivation below pH 4 was due to its irreversible denaturation, whereas the inactivation at higher pH was due to a true reversible pH effect on the enzyme velocity. Kinetic studies revealed that hydrogen ion acted as a substrate-directed activator of the free enzyme, but not the enzyme-substrate complex, with a molecular dissociation constant of 4 X 10(-6). The enzyme activity was not affected by unconjugated bile acids, primarily due to their extremely low water solubility. Conjugated bile acids, on the other hand, exerted heterogeneous and pH-dependent effects on the enzyme. At pH 5.2, taurocholic acid and glycocholic acid were substrate-directed activators of the enzyme; taurochenodeoxycholic acid and taurodeoxycholic acid, competitive inhibitors; and glycochenodeoxycholic acid and glycodeoxycholic acid, mixed inhibitors. At pH 7.0 all taurine and glycine conjugates behaved as substrate-directed activators. Though beta-glucuronidase activity at pH 7 was only 23% of its maximal activity at pH 5.2, conjugated bile acids tended to restore its activity to a certain extent at pH 7. Thus, endogenous beta-glucuronidase could play a significant role in pigment cholelithiasis.

Bile Acids and Salts↗