Comparative studies of bile salts, myxinol disulphate, the principal bile salt of hagfish (Myxinidae).
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ABSTRACT:
SUBMITTER: Haslewood GA
PROVIDER: S-EPMC1265115 | biostudies-other | 1966 Jul
REPOSITORIES: biostudies-other
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Project description:1. Material containing the less polar sulphate previously noticed in hagfish bile salts gave, after dioxan-trichloroacetic acid cleavage, 16-deoxymyxinol [3beta,7alpha,-26(27)-trihydroxy-5alpha-cholestane]. 2. Anodic coupling of 3beta-hydroxy-5beta-cholanoic acid and the mixed half esters of dl-methylsuccinic acid, followed by lithium aluminium hydride reduction, yielded 3beta,26(27)-dihydroxy-5beta-cholestane. 3. 16-Deoxymyxinol, the third known bile alcohol having the 3beta-hydroxy-5alpha-hydrogen configuration, poses again the question of how the 3beta-hydroxyl group of cholesterol can be ;retained' in biosynthesis of primitive bile salts.
| S-EPMC1187781 | biostudies-other
Project description: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 [alpha](D) measurements indicated that arapaimic acid and arapaimol-A and -B are respectively 2alpha,3alpha,7alpha,12alpha-tetrahydroxy-5beta,25in-cholestan-26-oic acid, 5beta,25R-cholestane-2beta,3alpha,7alpha,12alpha,26-pentol and 5beta-cholestane-2beta,3alpha,7alpha,12alpha,26,27-hexol. 3. Partial synthesis of 2beta,3alpha,7alpha,12alpha-tetrahydroxy-5alpha- and -5beta-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 C(27) acid; they are also specialized in showing 2beta-hydroxylation.
| S-EPMC1178539 | biostudies-other
Project description:1. Bile salts of Petromyzon marinus L. ammocoetes appeared to consist solely or chiefly of a crystalline substance, whose chromatographic and i.r.-spectral characteristics suggested that it was a monosulphate ester of a bile alcohol having the 3alpha,7alpha,12alpha-trihydroxy pattern of substitution in a 5alpha-steroid nucleus. 2. This substance on cleavage with dioxan-trichloroacetic acid gave petromyzonol, n.m.r. and mass-spectral examination of which suggested the structure 5alpha-cholane-3alpha,7alpha,12alpha,24-tetrol. 3. 3alpha,7alpha,12alpha-Trihydroxy-5alpha-cholanoic acid (allocholic acid) from the lizards Anolis lineatopus lineatopus Gray and Cyclura carinata Harlan (family Iguanidae) was esterified with propan-1-ol and reduced by lithium aluminium hydride to 5alpha-cholane-3alpha,7alpha,12alpha,24-tetrol, identical with petromyzonol. 4. Chromic acid oxidation of petromyzonol sulphate from lamprey bile, followed by acid hydrolysis, gave 24-hydroxy-5alpha-cholane-3,7,12-trione; hence the sulphate ester group is at C-24. 5. Petromyzonol sulphate is both primitive and unique: a study of its biogenesis might improve our understanding of evolution at the molecular level.
| S-EPMC1184842 | biostudies-other
Project description:1. Bile salts of the sturgeons Acipenser guldenstaedti Brandt, Acipenser stellatus Pall and Huso huso L. and of the paddlefish Polyodon spathula Walbaum are shown to be closely similar, consisting mainly of taurocholate with minor amounts of tauroallocholate and the monosulphates of bile alcohols. The bile alcohols, comprising less than 10% of the bile salts, are mixtures with high proportions of substances resembling C(27) tetrols and of C(27) pentols, including 5beta-cyprinol and (probably) 5alpha-cyprinol. 2. 5beta-Cyprinol (3alpha,7alpha,12alpha,26,27-pentahydroxy-5beta-cholestane) was made from cholic acid via 3alpha,7alpha,12alpha-triacetoxy-5beta-cholan-24-ol in an overall yield of about 0.8%. 3. The chemical nature of chondrostean bile salts agrees with the systematic position of the fishes and suggests further correspondence between evolution at the morphological and molecular levels.
| S-EPMC1198802 | biostudies-other
Project description:1. G.l.c. examination of bile alcohols prepared from the sucker Catostomus commersoni Lacépède (family Catostomidae) showed that although 5alpha-cyprinol (5alpha-cholestane-3alpha,7alpha,12alpha,26,27-pentol) was a minor constituent, the principal bile alcohol was an undescribed substance, probably present in the bile as the C-26 sulphate ester, whose i.r., n.m.r. and mass spectra agreed with the structure 5alpha-cholestane-3alpha,7alpha,12alpha,24,26-pentol. 2. M(D) studies suggest that this 5alpha-chimaerol is the 24(+), 25S enantiomer and that 5beta-chimaerol (chimaerol) from Chimaera monstrosa bile also has the 24(+), 25S configuration. These findings imply that bile alcohol biosynthesis in suckers and chimaeras includes stereospecific oxidation of cholesterol at C-26. 3. C. commersoni bile acids (present in minor amounts) probably consist largely of 3alpha,7alpha,12alpha-trihydroxy-5alpha-cholan-24-oic acid (allocholic acid). 4. 5alpha-Chimaerol sulphate and 5alpha-cyprinol sulphate are probably biochemically equivalent as bile salts, and can be considered as arising by parallel evolution.
| S-EPMC1185402 | biostudies-other
Project description:Protein denaturation is under intensive research, since it leads to neurological disorders of severe consequences. Avoiding denaturation and stabilizing the proteins in their native state is of great importance, especially when proteins are used as drug molecules or vaccines. It is preferred to add pharmaceutical excipients in protein formulations to avoid denaturation and thereby stabilize them. The present study aimed at using bile salts (BSs), a group of well-known drug delivery systems, for stabilization of proteins. Bovine serum albumin (BSA) was taken as the model protein, whose association with two BSs, namely sodium cholate (NaC) and sodium deoxycholate (NaDC), was studied. Denaturation studies on the pre-formed BSA-BS systems were carried out under chemical and physical denaturation conditions. Urea was used as the chemical denaturant and BSA-BS systems were subjected to various temperature conditions to understand the thermal (physical) denaturation. With the denaturation conditions prescribed here, the data obtained is informative on the association of BSA-BS systems to be hydrophobic and this effect of hydrophobicity plays an important role in stabilizing the serum albumin in its native state under both chemical and thermal denaturation.
| S-EPMC5859114 | biostudies-literature
Project description:Background & aimsIntestine-restricted inhibitors of the apical sodium-dependent bile acid transporter (ASBT, or ileal bile acid transporter) are approved as treatment for several inheritable forms of cholestasis but are also associated with abdominal complaints and diarrhoea. Furthermore, blocking ASBT as a single therapeutic approach may be less effective in moderate to severe cholestasis. We hypothesised that interventions that lower hepatic bile salt synthesis in addition to intestinal bile salt uptake inhibition provide added therapeutic benefit in the treatment of cholestatic disorders. Here, we test combination therapies of intestinal ASBT inhibition together with obeticholic acid (OCA), cilofexor, and the non-tumorigenic fibroblast growth factor 15 (Fgf15)/fibroblast growth factor 19 (FGF19) analogue aldafermin in a mouse model of cholestasis.MethodsWild-type male C57Bl6J/OlaHsd mice were fed a 0.05% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and received daily oral gavage with 10 mg/kg OCA, 30 mg/kg cilofexor, 10 mg/kg ASBT inhibitor (Linerixibat; ASBTi), or a combination. Alternatively, wild-type male C57Bl6J/OlaHsd mice were injected with adeno-associated virus vector serotype 8 (AAV8) to express aldafermin, to repress bile salt synthesis, or to control AAV8. During a 3-week 0.05% DDC diet, mice received daily oral gavage with 10 mg/kg ASBTi or placebo control.ResultsCombination therapy of OCA, cilofexor, or aldafermin with ASBTi effectively reduced faecal bile salt excretion. Compared with ASBTi monotherapy, aldafermin + ASBTi further lowered plasma bile salt levels. Cilofexor + ASBTi and aldafermin + ASBTi treatment reduced plasma alanine transaminase and aspartate transaminase levels and fibrotic liver immunohistochemistry stainings. The reduction in inflammation and fibrogenesis in mice treated with cilofexor + ASBTi or aldafermin + ASBTi was confirmed by gene expression analysis.ConclusionsCombining pharmacological intestinal bile salt uptake inhibition with repression of bile salt synthesis may form an effective treatment strategy to reduce liver injury while dampening the ASBTi-induced colonic bile salt load.Impact and implicationsCombined treatment of intestinal ASBT inhibition with repression of bile salt synthesis by farnesoid X receptor agonism (using either obeticholic acid or cilofexor) or by expression of aldafermin ameliorates liver damage in cholestatic mice. In addition, compared with ASBT inhibitor monotherapy, combination treatments lower colonic bile salt load.
| S-EPMC10701132 | biostudies-literature
Project description:The fish olfactory receptor ORA family is orthologous to the mammalian vomeronasal receptors type 1. It consists of six highly conserved chemosensory receptors expected to be essential for survival and communication. We deorphanized the zebrafish ORA family in a heterologous cell system. The six receptors responded specifically to lithocholic acid (LCA) and closely related C24 5β-bile acids/salts. LCA attracted zebrafish as strongly as food in behavioral tests, whereas the less potent cholanic acid elicited weaker attraction, consistent with the in vitro results. The ORA-ligand recognition patterns were probed with site-directed mutagenesis guided by in silico modeling. We revealed the receptors' structure-function relationship underlying their specificity and selectivity for these compounds. Bile acids/salts are putative fish semiochemicals or pheromones sensed by the olfactory system with high specificity. This work identified their receptors and provided the basis for probing the roles of ORAs and bile acids/salts in fish chemosensation.
| S-EPMC6497948 | biostudies-literature
Project description:1. The bile salts of three frog species of the genus Ptychadena and of Rana catesbeiana have been compared with those of their tadpoles. For R. catesbeiana comparison was made of the bile salts in at least ten of the recognized stages of tadpole metamorphosis. 2. In all cases, adult bile salts were more complex than those of the tadpoles. 3. In R. catesbeiana after stage 18, 26-deoxy-5 alpha-ranol was hydroxylated to form 5 alpha-ranol (27-nor-5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 24 xi, 26-pentol) and at least two other bile alcohols appeared in solvolysed bile salts. 4. Tadpole bile salts were not found to be biochemically more primitive than those of fully metamorphosed frogs; in some, but not all, cases tadpole bile alcohols could be regarded as biochemical precursors of those in the adult frogs. 5. Detailed evidence for the structure of the bile salts from mass-spectral fragmentation patterns has been deposited as Supplementary Publication SUP 50097 (2 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.
| S-EPMC1161630 | biostudies-other
Project description:Enterohemorrhagic Escherichia coli (EHEC), including serotype O157:H7, cause severe food-borne illness. On route to the human colon, they encounter and resist, numerous anti-microbial ingestion stresses. We hypothesize that these stresses cue EHEC to alter virulence properties. This study investigated the impact of bile salts on virulence properties and examined the genetic basis of the phenotypes. Established assays were used to examine adhesion to human epithelial cells, motility, verotoxin (VT) production and antimicrobial resistance with/without bile salt stress. Bacteria treated for 90 minute in DMEM plus 0.15% (w/v) bile salt mix demonstrated significantly enhanced adhesion to epithelial cells and resistance to several antibiotics but did not increase motility or VT production. To determine the genetic basis of these phenotypes a microarray experiment was conducted. EHEC strain 86-24, in mid-log phase of growth, were grown in DMEM pH 7.4 (control), or DMEM plus bile salt mix (0.15% w/v), for 90 minutes, statically at 37˚C, 5% CO2 prior to harvesting RNA for the microarray study. Four biological replicates were produced for each treatment. Microarray and gene expression analysis (semi-quantitative RT-PCR and beta-galactosidase reporter assays) of bile salt-treated EHEC revealed significant up-regulation of genes for lipid A modification, fimbriae, an efflux pump, and a two-component regulatory system relative to the bacteria grown in DMEM alone. This work points to several mechanisms that EHEC employs to resist the stresses of the human small intestine, notably efflux, antimicrobial resistance, and outer membrane alterations. Bile salts enhanced the virulence-related properties of increased adhesion and resistance to antimicrobials but not VT production or motility. This research contributes to our understanding of how EHEC senses and responds to host environmental signals and the mechanisms this pathogen uses to successfully colonize and infect the human host.
2011-09-06 | GSE22060 | GEO