Inhibition of cholesterol synthesis from mevalonate by aminotriazole treatment in vivo

3-Amino-1,2,4-triazole (aminotriazole) is an irreversible inhibitor of catalase which is a marker enzyme of peroxisomes. We studied the effect of aminotriazole treatment on biosyntheses of cholesterol and bile acid in vivo. When catalase activity of peroxisomes of rat liver was inhibited by aminotriazole treatment, bile acid content in the bile was significantly decreased to about 70% of the control, but that in the liver was not changed. Cholesterol content in the bile was significantly decreased to about 80% of the control, while in liver and serum the content was not significantly changed. When [2-14C]mevalonate was administered to rats, radioactivities of cholesterol in the liver, serum and bile were all drastically decreased by aminotriazole treatment, and an unidentified radioactive product was detected. Radioactivity of bile acid in the bile was also greatly decreased. In a similar experiment with [4-14C]cholesterol, aminotriazole treatment had no effect on the radioactivity of either cholesterol or bile acid in the liver, serum and bile. In this case, the unidentified product could not be detected. These results indicate that when catalase activity of liver peroxisomes is suppressed by aminotriazole treatment, biosynthesis of bile acid from exogenous cholesterol is not inhibited, but a step in the pathway of biosynthesis of endogenous cholesterol from mevalonate is inhibited.     

Potential bile acid metabolites. XV. Synthesis of 4 beta-hydroxylated bile acids; unique bile acids in human fetal bile

The 4 beta-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) beta-face cis-dihydroxylation of delta 3 intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3 beta,4 beta-diols followed by oxidation of the resulting 4 beta-monocathylates, or direct selective oxidation at C-3 of 3 beta,4 beta-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4 beta-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3 beta-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.     

High-performance liquid chromatographic analysis of bile acids in hamster bile

A high-performance liquid chromatographic procedure has been developed for the determination of pentamidine concentrations in serum samples. A microbore, reversed-phase column was used with a mobile phase consisting of methanol and water with sodium heptanesulfonate and triethylamine as modifiers. Pentamidine could be extracted from serum only by the addition of an ion-pairing agent, di(2-ethylhexyl) phosphoric acid, to the chloroform used for extraction. The method can be used to reliably detect levels as low as 5 ng/ml. The pentamidine concentration in the serum of eleven patients 24 h after their tenth daily dose of pentamidine averaged 60 +/- 34 ng/ml.     

Recognition of bile acids at cyclodextrin-modified gold electrodes.

Lipoylamino-beta- and gamma-cyclodextrin (LP-beta-CD and LP-gamma-CD, respectively) were adsorbed at the surface of gold electrodes by sulfur-gold bonding. The resultant electrodes exhibited quasi-reversible voltammograms for the redox reaction of Fe(CN)6(3-/4-) in aqueous solutions, with peak-to-peak separation (deltaEp) being 85 mV at 20 mV s(-1) as a potential sweep rate. When bile acids are added to the solution, deltaEp values increased to 200-300 mV with increasing the concentration of bile acids. A Langmuir-type adsorption analyses satisfactorily afforded the binding constants (Ksurf) of the surface-confined LP-beta-CD and LP-gamma-CD with the bile acids. The obtained Ksurf values of LP-gamma-CD are 5.0-50 times larger than the corresponding binding constants of gamma-CD in homogeneous aqueous solutions. Cyclic voltammetric experiments with positively, negatively, and non-charged adamantane derivatives as well as pH titration experiments revealed that the retardation of the electrode reaction of negatively charged Fe(CN)6(3-/4-) caused by bile acids was attributable (1) to electric potential changes due to the accumulation of the negative charges at the electrode surface, and (2) to an increase in the hydrophobicity of the electrode surface due to the binding of hydrophobic bile acids to the LP-beta-CD and LP-gamma-CD membranes.     

Biomaterials made of bile acids

The use of natural compounds in the preparation of new materials can improve the biocompatibility of the materials and avoid any potential toxicity of the degradation products when used for biomedical applications. Bile acids are amphiphilic molecules biosynthesized in the liver. They are used to prepare various polymers and oligomers. These polymers made of bile acids are promising materials in both biomedical and pharmaceutical fields.     

基于胆酸的功能性分子的研究进展

胆酸是存在于人和动物体内的天然分子,由胆固醇在肝脏中合成．其结构上具有亲水的一面和憎水的一面,以其作为结构单元可以合成各种各样的功能性分子．这些分子因其独特的物理化学特性,被广泛应用到化学、生物医学等领域．本文回顾了近几年来国内外研究人员以胆酸为结构单元合成的高分子和低聚物及这些分子在生物医用材料方面的应用．     

Characterization of bile acids and fatty acids from ox bile in oil paintings by gas chromatography-mass spectrometry

Characterization of ox bile, traditionally used in painting, is of interest in the fields of archaeometry and conservation and restoration of works of art. Bile acids, fatty acids (F), and cholesterol found in ox bile have been identified using a derivatization method that combines the formation of ethyl esters from the carboxylic groups and the trimethylsilyl ethers from hydroxyl groups. This method of analysis is consistent with these others proposed by the authors to analyze drying oils, proteins, and diterpenic resins usually used as binders and varnishes by the painters. Bile acids from binary samples such as animal glue/ox bile, casein/ox bile and Arabic gum/ox bile have been successfully analyzed using the proposed method. Finally, a method of analysis of mixtures of drying oil and ox bile has been also proposed attempting to quantitatively characterize samples in which ox bile was added to the drying oil for increasing the surfactant properties.     

Charge-remote fragmentation of taurine-conjugated bile acids

Taurine-conjugated bile acids are an important group of biological metabolites. When investigated by negative-ion fast-atom bombardment collision-induced dissociation mass spectroscopy they show charge-remote fragmentations of the [M-H]- pseudomolecular ion. These fragmentations provide information on the positions of ring substituents remote from the charge site. In the present work we have compared the negative-ion fast-atom bombardment collision-induced dissociation spectra of six different conjugated bile acids.