| Reference | [1]. J Lipid Res. 1985 Dec;26(12):1431-7.<br />
Formation and secretion of glycolithocholate-3-sulfate in primary hepatocyte cultures.<br />
Kirkpatrick RB, Belsaas RA.<br />
Bile acid sulfation was studied in primary hepatocyte cultures. The primary hepatocyte cultures formed glycolithocholate-3-sulfate (GLC-S) when glycolithocholate (GLC) was added to the medium. The relative percentage of GLC-S formation increased when the GLC concentration was increased from 10 microM to 100 microM. GLC-S formation was linear to 60 min. GLC-S secretion into the medium was detectable at 75 min and linear to 8 hr. In contrast to the effect of GLC concentration, there was no difference in GLC-S formation or secretion when inorganic sulfate in the medium was increased 16-fold (100 microM-1600 microM). We conclude that the rate of bile acid sulfate formation in cultured primary hepatocytes is primarily controlled by bile acid, but not inorganic sulfate, concentration.<br />
PMID: 4086945 [Indexed for MEDLINE]<br />
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[2]. Biochim Biophys Acta. 1979 Oct 26;575(1):16-26. doi: 10.1016/0005-2760(79)90126-7.<br />
Solution properties of sulfated monohydroxy bile salts. Relative insolubility of the disodium salt of glycolithocholate sulfate.<br />
Carey MC, Wu SF, Watkins JB.<br />
Physical-chemical properties of the major sulfated monohydroxy bile salts of man are described. In general, the sulfates are significantly more water-soluble than the non-sulfated species as a result of lower critical micellar temperatures, high aqueous monomeric solubilities and critical micellar concentrations. Nevertheless, at 37 degrees C the disodium salt of glycolithocholate sulfate, the major monohydroxy bile salt of man is not more soluble than its non-sulfated form. Since aqueous solubility correlates inversely with the cholestatic potential of bile salts, our results suggest that this sulfate may be potentially hepatoxic. Micellar solubility of phosphatidylcholine and cholesterol by the majority of non-sulfated and sulfated monohydroxy bile salts is slight. Nonetheless, phosphatidylcholine is very well solubilized by taurolithocholate sulfate but cholesterol solubility is not increased appreciably. Cholesterol saturation in model bile systems of taurochenodeoxycholate and phosphatidylcholine is impaired by the addition of sulfated lithocholate conjugates but with physiological bile salt compositions this reduction is not significant.<br />
DOI: 10.1016/0005-2760(79)90126-7 PMID: 508777 [Indexed for MEDLINE]<br />
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[3]. J Lipid Res. 1986 Nov;27(11):1111-23.<br />
Evidence for an ordered reaction mechanism for bile salt: 3'phosphoadenosine-5'-phosphosulfate: sulfotransferase from rhesus monkey liver that catalyzes the sulfation of the hepatotoxin glycolithocholate.<br />
Barnes S, Waldrop R, Crenshaw J, King RJ, Taylor KB.<br />
The in vivo formation of the sulfate ester of glycolithocholate is a critical step in the elimination of this hepatotoxic bile salt. Rhesus monkeys fed chenodeoxycholate or ursodeoxycholate, the precursors of lithocholate, develop frank cirrhosis in association with accumulation of nonsulfated glycolithocholate in bile. An enzyme catalyzing the formation of glycolithocholate-3-sulfate has been isolated from hepatic cytosol of adult female rhesus monkeys and has been purified 146-fold. When reduced it appears as a 30 kD band on an SDS-polyacrylamide gradient gel. It has a pH optimum of 7.0 and is stimulated by low concentrations of Mg2+ (up to 2 mM), but does not have an absolute requirement for this metal ion. The kinetics of this enzyme have been investigated to ascertain whether its reaction mechanism can account for the poor in vivo rate of glycolithocholate sulfation. Inhibitor studies with an oxidized metabolite of lithocholate, 3-keto-5 beta-cholanoate, showed that the latter is a competitive inhibitor of glycolithocholate and is noncompetitive with the active form of sulfate, 3'phosphoadenosine-5'-phosphosulfate. The monophosphonucleotide 3'-AMP is a competitive inhibitor of 3'phosphoadenosine-5'-phosphosulfate, and is noncompetitive with glycolithocholate. These observations are consistent with a sequentially ordered Bi Bi reaction mechanism in which the bile salt is the first substrate to bind to the enzyme. Such a reaction mechanism for bile salt:3'phosphoadenosine-5'-phosphosulfate:sulfotransferase would be, therefore, the first time in which the sulfate acceptor (the bile salt) is the initial substrate to bind to a sulfotransferase. These studies have shown that although rhesus monkeys have a liver enzyme capable of forming the sulfate ester of glycolithocholate, its reaction mechanism and the potent inhibition caused by simple metabolites, such as 3-keto-5 beta-cholanoate, may serve to under-express the activity of the enzyme in vivo.<br />
PMID: 3470420 [Indexed for MEDLINE]<br />
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[4]. PLoS One. 2015 Nov 6;10(11):e0142610. doi: 10.1371/journal.pone.0142610. eCollection 2015.<br />
Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study.<br />
Alonso A(1), Yu B(2), Qureshi WT(3), Grams ME(4)(5), Selvin E(5)(6), Soliman EZ(7)(8), Loehr LR(9), Chen LY(10), Agarwal SK(11), Alexander D(12), Boerwinkle E(2)(13).<br />
Author information: (1)Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America. (2)Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, United States of America. (3)Division of Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America. (4)Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. (5)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. (6)Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, United States of America. (7)Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America. (8)Department of Medicine-Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America. (9)Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America. (10)Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America. (11)Mount Sinai Heart Hospital, New York, New York, United States of America. (12)Metabolon, Inc., Durham, North Carolina, United States of America. (13)Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America.<br />
BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited. METHODS: We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987-1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates. RESULTS: During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12-1.32) for glycolithocholate sulfate and 1.22 (1.10-1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes. CONCLUSION: We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted.<br />
DOI: 10.1371/journal.pone.0142610 PMCID: PMC4636390 PMID: 26544570 [Indexed for MEDLINE]<br />
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[5]. J Lipid Res. 1977 Jul;18(4):491-5.<br />
Synthesis of sulfate esters of lithocholic acid, glycolithocholic acid, and taurolithocholic acid with sulfur trioxide-triethylamine.<br />
Tserng KY, Klein PD.<br />
The facile synthesis of lithocholic acids sulfates by a procedure that produced the desired products in over 90% yield is described. Lithocholic acid sulfate and glycolithocholic acid sulfate were synthesized by reacting lithocholic acid or glycolithocholic acid with sulfur trioxide-triethylamine complex in dimethylformamide for 0.5-1 hr. Taurolithocholic acid sulfate was obtained by conjugating lithocholic acid sulfate with taurine in dimethylformamide at 90 degrees C for 0.5 hr. The one-pot synthesis of taurolithocholic acid sulfate starting from lithocholic acid is also described. This procedure, which generated lithocholic acid sulfate in situ, produced taurolithocholic acid sulfate in 98% yield, compared to an overall yield of less than 10% obtained by previously published procedures.<br />
PMID: 894140 [Indexed for MEDLINE]
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