scholarly journals A more detailed study of bile salt evolution, including techniques for small-scale identification and their application to amphibian biles

1974 ◽  
Vol 141 (2) ◽  
pp. 485-494 ◽  
Author(s):  
Ian G. Anderson ◽  
Geoffrey A. D. Haslewood ◽  
Robert S. Oldham ◽  
Bernard Amos ◽  
Laszlo Tökés

1. Methods have been developed for the isolation and identification of small amounts of bile salts and of bile acids and alcohols obtained by solvolysis. These methods involve preparative and analytical t.l.c., purification on columns of protonated Al2O3 and Sephadex LH-20 and also g.l.c.–mass spectroscopy of solvolysis products. 2. Application to 29 species of frogs and toads has confirmed the constancy of bile salt patterns in a single species, including colour phases in two instances, and has revealed great variations between different species in some genera (e.g. Rana, Ptychadena) and little difference between widely distributed species in others (e.g. Bufo). 3. Taxonomic deductions should be made with caution and with regard to the physiological significance of the biochemical character considered. The molecular differences found might be interpreted as indicating variations in the rate of evolution.

1972 ◽  
Vol 126 (5) ◽  
pp. 1161-1170 ◽  
Author(s):  
G. A. D. Haslewood ◽  
L. Tökés

1. Arapaima gigas bile salts were hydrolysed by alkali or cleaved with dioxan–trichloroacetic acid to give cholic acid, arapaimic acid, arapaimol-A and arapaimol-B. 2. I.r., n.m.r. and mass spectroscopy and [α]D measurements indicated that arapaimic acid and arapaimol-A and -B are respectively 2α,3α,7α,12α-tetrahydroxy−5β,25∈-cholestan-26-oic acid, 5β,25R-cholestane-2β,3α,7α,12α,26-pentol and 5β-cholestane-2β,3α,7α,12α,26,27-hexol. 3. Partial synthesis of 2β,3α,7α,12α-tetrahydroxy−5α- and −5β-cholan-24-oic acid and their spectral examination fully confirmed these conclusions. 4. A. gigas bile salts show primitive features in that they comprise alcohol sulphates and a C27 acid; they are also specialized in showing 2β-hydroxylation.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Stephen D Lee ◽  
Sheila J Thornton ◽  
Kishor M Wasan

Rationale: Removal of bile salts from the liver is the final step of the reverse cholesterol transport pathway. We studied the contribution of Abcb1 (P-glycoprotein), in bile acid efflux. Although a number of endogenous substrates have been postulated for Abcb1 based on in vitro evidence, studies using animal models have not supported these claims. Recent studies in mice demonstrated that in the absence of the Bile Salt Efflux Pump (Bsep), Abcb1 is required for removal of bile salts, especially when challenged with a cholic acid containing diet. To date, no study using atherogenic diets has demonstrated the role of Abcb1 in the removal of bile salts in the presence of functional Bsep. Methods: We fed male mice lacking both isoforms of Abcb1 (Abcb1a -/- /1b -/- ) and wild-type controls a diet providing either 25% or 45% of the kcal from fat, supplemented with either normal chow or high levels of cholesterol (0.02% w/w or 0.2% w/w respectively) for nine weeks; n=5 per group. On the tenth week, we assessed the efflux of cholesterol, phospholipid and bile acids to the gallbladder. Enzymatic assays were used to measure cholesterol and phospholipid, the pool of bile acids was quantified by HPLC to determine the concentrations of the six most prevalent murine bile acids. Results: Abcb1 knockout mice have a >30% reduction in the moles of bile salt normalized to phospholipid relative to wild type mice after administration of diets containing either elevated fat or cholesterol (p<0.05). Neither the efflux of phospholipid, nor the molar composition of the six bile acids was affected by deletion of Abcb1. Conclusions: We conclude that Abcb1 is a secondary efflux mechanism required for the removal of bile acids after consumption of diets rich in fat and/or cholesterol. Although Abcb1 knockout mice have reduced total bile acids in the gallbladder, the molar ratio of the specific bile acids is the same as in the wild type mice. These data suggest that Abcb1 effluxes the six bile acids in a non-specific manner, unlike Bsep which preferentially effluxes hydrophobic bile acids. The lack of specificity demonstrated by Abcb1 is desirable for a low- affinity secondary efflux mechanism, which supplements Bsep activity in bile acid output. Acknowledgments: Canadian Institutes of Health Research, Michael Smith Foundation for Health Research


2003 ◽  
Vol 17 (4) ◽  
pp. 265-271 ◽  
Author(s):  
Richard N Redinger

The coordinated effect of lipid activated nuclear hormone receptors; liver X receptor (LXR), bound by oxysterol ligands and farnesoid X receptor (FXR), bound by bile acid ligands, act as genetic transcription factors to cause feed-forward cholesterol catabolism to bile acids and feedback repression of bile acid synthesis, respectively. It is the coordinated action of LXR and FXR, each dimerized to retinoid X receptor, that signal nuclear DNA response elements to encode proteins that prevent excessive cholesterol accumulation and bile salt toxicity, respectively. LXR helps prevent hypercholesterolemia by enhancing transporters for cholesterol efflux that enhance reverse cholesterol transport, while FXR enhances intestinal reabsorption and preservation of bile salts by increasing the ileal bile acid binding protein. FXR also targets sodium taurocholate cotransport peptide and bile salt export pump (protein) genes to limit bile salt uptake and enhance export, respectively, which prevents bile salt toxicity. Other nuclear hormone receptors such as pregnan X receptor, which share the obligate partner, retinoid X receptor, and vitamin D receptor also function as bile acid sensors to signal detoxification by hydroxylation of toxic bile acids. Pharmacologically targeted receptor agonists (or antagonists) may be developed that alter cholesterol and bile salt concentrations by modulating nuclear hormone receptors and/or their coactivators or corepressors to positively affect cholesterol homeostasis and bile salt metabolism. It is the coordinated transcription factor action of LXR, which responds to ligand binding of circulating oxysterols in both liver and peripheral tissues, and FXR responding to bile salts within the enterohepatic circulation that make possible the regulation of cholesterol and bile acid homeostasis.


1999 ◽  
Vol 62 (12) ◽  
pp. 1461-1465 ◽  
Author(s):  
ABDELHAMID KERKADI ◽  
CLAUDE BARRIAULT ◽  
RONALD R. MARQUARDT ◽  
ANDRZEJ A. FROHLICH ◽  
IBRAHIM M. YOUSEF ◽  
...  

We have shown that the addition of cholestyramine (CHA, a resin known to bind bile salts in the gastrointestinal tract) to ochratoxin A (OTA)-contaminated rat diets reduced plasma levels of the toxin and prevented OTA-induced nephrotoxicity. To elucidate the mechanism of action of CHA, we carried out in vitro experiments to determine whether the resin may bind the toxin. For comparative purposes, binding of bile salts to the resin was also examined. Results showed that CHA binds both OTA and bile salts (taurodeoxycholate [TDC] and taurocholate [TCA]). Also, CHA showed greater affinity for OTA and TDC than for TCA. At 1 mM concentration, 96% of OTA and 80% of TDC were bound to the resin, while for TCA binding was only 50%. However, saturation of the resin was reached at higher levels with bile acids compared to OTA (3.67 mmol/g resin for TCA and 3.71 mmol/g resin for TDC versus 2.85 mmol/g resin for OTA). To characterize the nature of the binding of the toxin to CHA, NaCl (0 to 200 mM) was added to a fixed amount of OTA or bile acids. As expected, TCA absorption was decreased by the addition of NaCl (&lt;50 mM), indicating electrostatic binding. However, OTA and TDC sorption was decreased only at high concentrations of NaCl (&gt;150 mM), suggesting a stronger binding to the resin than that shown with TCA. Sequential competitive studies demonstrated that CHA binds more OTA than TCA. The results of the in vivo study show the role of bile salts in OTA absorption. The toxin's plasma levels at 1 and 3 h after a single oral dose of OTA were significantly decreased in bile salt–depleted rats compared to the control. Thus, the alteration of the bile salt biliary pool and OTA enterohepatic circulation may be an additional mechanism of action of the resin against mycotoxin toxicity.


2019 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Nurul Octavia Wasis ◽  
Nyoman Semadi Antara ◽  
Ida Bagus Wayan Gunam

Tabah bamboo shoot pickle is one of the fermented food which is the source of lactic acid bacteria.  Lactic acid bacteria (LAB) is beneficial to health because it has the ability as a probiotic. Lactic acid bacteria that have probiotic criteria should have resistance to low pH and bile salts. This study aims to determine isolates of lactic acid bacteria isolated from tabah bamboo shoot pickle resistant to low pH and bile salts (NaDC). Lactic acid bacteria were tested to low pH by using MRS broth that have different pH (pH 2, pH 3, pH 4 and pH 6.2 as a control) incubated at 37ºC for 3 hours. isolates were survive in low pH then continued in bile salt resistance test with 0.3% bile salt concentration for 15 minutes, 30 minutes, 45 minutes, 60 minutes and 24 hours. The results showed that three isolates out of 88 isolates had ability to grow in low pH and in medium supplemented by NaDC 0,3%. The isolates are AR 3057, AR 3101 and AR 6152 which can be used as candidat of  probiotic. Keywords : Tabah bamboo shoot pickle, lactic acid bacteria, probiotic, low pH, bile salt


1997 ◽  
Vol 321 (2) ◽  
pp. 389-395 ◽  
Author(s):  
Charles M. G. FRIJTERS ◽  
Roelof OTTENHOFF ◽  
Michel J. A. van WIJLAND ◽  
Carin M. J. van NIEUWKERK ◽  
Albert K. GROEN ◽  
...  

The phosphatidyl translocating activity of the mdr2 P-glycoprotein (Pgp) in the canalicular membrane of the mouse hepatocyte is a rate-controlling step in the biliary secretion of phospholipid. Since bile salts also regulate the secretion of biliary lipids, we investigated the influence of the type of bile salt in the circulation on mdr2 Pgp expression and activity. Male mice were fed a purified diet to which either 0.1% (w/w) cholate or 0.5% (w/w) ursodeoxycholate was added. This led to a near-complete replacement of the endogenous bile salt pool (mainly tauromuricholate) by taurocholate or tauroursodeoxycholate respectively. The phospholipid secretion capacity was then determined by infusion of increasing amounts of tauroursodeoxycholate. Cholate feeding resulted in a 55% increase in maximal phospholipid secretion compared with that in mice on the control diet. Northern blotting revealed that cholate feeding increased mdr2 Pgp mRNA levels by 42%. Feeding with ursodeoxycholate did not influence the maximum rate of phospholipid output or the mdr2 mRNA content. Female mice had a higher basal mdr2 Pgp mRNA level than male mice, and this was also correlated with a higher phospholipid secretion capacity. This could be explained by the 4-fold higher basal cholate content in the bile of female compared with male mice. Our results suggest that the type of bile salts in the circulation influences the expression of the mdr2 gene.


1994 ◽  
Vol 299 (3) ◽  
pp. 665-670 ◽  
Author(s):  
G Fricker ◽  
V Dubost ◽  
K Finsterwald ◽  
J L Boyer

The substrate specificity for the transporter that mediates the hepatic uptake of organic anions in freshly isolated hepatocytes of the elasmobranch little skate (Raja erinacea) was determined for bile salts and bile alcohols. The Na(+)-independent transport system exhibits a substrate specificity, which is different from the specificity of Na(+)-dependent bile salt transport in mammals. Unconjugated and conjugated di- and tri-hydroxylated bile salts inhibit uptake of cholyltaurine and cholate competitively. Inhibition is significantly greater with unconjugated as opposed to glycine- or taurine-conjugated bile salts. However, the number of hydroxyl groups in the steroid moiety of the bile salts has only minor influences on the inhibition by the unconjugated bile salts. Since the transport system seems to represent an archaic organic-anion transport system, other anions, such as dicarboxylates, amino acids and sulphate, were also tested, but had no inhibitory effect on bile salt uptake. To clarify whether bile alcohols, the physiological solutes in skate bile, share this transport system, cholyltaurine transport was studied after addition of 5 beta-cholestane-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. These bile alcohols inhibit cholyltaurine uptake non-competitively. In contrast, uptake of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, which is Na(+)-independent, is not inhibited by cholyltaurine. The findings further characterize a Na(+)-independent organic-anion transport system in skate liver cells, which is not shared by bile alcohols and has preference for unconjugated lipophilic bile salts.


2019 ◽  
Vol 174 ◽  
pp. 493-500 ◽  
Author(s):  
Julieta N. Naso ◽  
Fernando A. Bellesi ◽  
Víctor M. Pizones Ruiz-Henestrosa ◽  
Ana M.R. Pilosof

1984 ◽  
Vol 64 (4) ◽  
pp. 1055-1102 ◽  
Author(s):  
R. C. Strange

The hepatocyte is a polar cell that can remove a variety of molecules from blood and excrete them into bile. This review is primarily concerned with the mechanism of transport of the principal anions--the bile salts--across the sinusoidal membrane, their passage through the cell, and excretion across the canalicular membrane. Clearly much of this process is poorly understood, but the study of the membrane stages should be facilitated by the ability to prepare purified sinusoidal and canalicular membrane vesicles. For example, the relative importance of albumin-binding sites as well as the putative bile salt receptor proteins can be better assessed. It seems likely that although the interaction of bile salts with receptor proteins is important, it is an initial event that puts the bile salt in the correct place for uptake to occur. The driving force for uptake is the Na+ gradient created across the basolateral membrane by the activity of the Na+-K+-ATPase. Within the cell, various modes of transport have been suggested. Several authors emphasize the importance of protein binding of bile salts, either because of their presumed ability to maintain the concentration of these anions in the hepatocyte below their critical micellar concentration or because of their putative role in transport. It is important to understand these aspects of the role of cytosolic proteins for several reasons. Knowledge of the true concentration of free bile salt within the cell should allow estimation of whether the electrochemical gradient is sufficient for bile salts to accumulate in bile without the need for active transport of molecules from the cell into the canaliculus. The compartmental model described by Strange et al. (153) offers one theoretical way of determining the concentration of free bile salt, although the problems inherent in studying amphipath binding to the membranes of subcellular organelles (31) require that the model be reevaluated by the hygroscopic-desorption method. The second role suggested for the cytosolic bile salt-binding proteins is as transport proteins. As discussed in section VI, I think it is unlikely that the proteins identified so far act in this way, and it is more likely that movement occurs by diffusion in free solution. It is also important to determine the possible involvement of subcellular organelles such as Golgi bodies. Little is known of their role in the transport of bile salts or indeed where bile salt micelles are formed.(ABSTRACT TRUNCATED AT 400 WORDS)


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