PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “CHOLIC ACID”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMedDate not supplied

Enhanced transepithelial transport of peptides by conjugation to cholic acid.

The potential of the intestinal bile acid transporter to serve as a shuttle for small peptide molecules was investigated. Eleven peptides with a 2-6 amino acid backbone were conjugated to the 24-position of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oic acid (cholic acid) via an amide bond using an automated peptide synthesizer. In a human intestinal cell line (CaCo-2), cholic acid-peptide conjugates were able to inhibit the transepithelial transport of [3H]taurocholic acid, a natural substrate for the bile acid carrier, at a 100:1 conjugate/substrate ratio. Affinity for the carrier decreased significantly when the conjugate in the 24-position increased from 1 to 2 amino acids. Further increase in the amino acid chain length caused only minor decrease in affinity. A tetrapeptide-bile acid conjugate, [3H]-ChEAAA (Ch = cholic acid), was transported by the bile acid transporter, showing markedly higher apical (AP)-to-basolateral (BL) compared to BL-to-AP transport and inhibition by a 100-fold excess taurocholic acid. Another conjugate with 6 amino acids (ChEASASA) was transported by a passive diffusion pathway but still showed higher transport rates than the passive permeability marker mannitol, suggesting the possibility that the cholic acid moiety aids the passive membrane transfer of peptide molecules by increasing its lipophilicity. Metabolism of bile acid-peptide conjugates in CaCo-2 cells was 3% over 3 h. In conclusion, these studies show that the coupling of peptides to the 24-position of the sterol nucleus in cholic acid results in a combination of decreased metabolism and increased intestinal absorption, either by a carrier-mediated pathway or by accelerated passive diffusion.

Biological Transport↗
PubMed1994

Non-stereoselective formation of 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid during cholic acid biosynthesis.

Incubation of (25RS)-, (25R)- and (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA, 6, 6a, 6b) and (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid (7) with rat liver mitochondria gave all four stereoisomers (9a,9b,9c,9d) of 3 alpha,7 alpha,12 alpha,24-Tetrahydroxy-5 beta-cholestan-26-oic acid (TeHCA). The corresponding 27-nor analogs (10,11) were also converted non-stereoselectively to a 1:1 mixture of the epimeric 24-hydroxy compounds (12).

Animals↗
PubMed1992

Configuration of the 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid, an intermediate in the peroxisomal conversion of 3 alpha,7 alpha,12-trihydroxy-5 beta-cholestanoic acid to cholic acid in rat liver.

3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid, formed in the peroxisomal oxidation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl-CoA by the THCA-CoA oxidase in rat liver, was isolated and purified on reverse phase HPLC. The configuration of the C-24/25 double bond was determined to be trans (E) by using 1H-NMR spectrometry.

Animals↗
PubMed1983

Liver function and the diagnostic significance of conjugated cholic acid and chenodeoxycholic acid in serum of African patients with sickle cell disease.

Concentrations of two primary bile acids (cholic acid and chenodeoxycholic acid) were determined by radioimmunoassay in the serum of 15 African homozygous sickle cell patients, ages ranging from 4 to 22 years. The mean serum levels of the two primary bile acids studied were significantly elevated when compared with the normal mean values. About 67% of the patients had pathological elevation of both primary bile acids, thereby indicating some hepatobiliary damage. Serum conjugated cholic acid correlated significantly with serum chenodeoxycholic acid in the sickle cell disease (r = 0.91, p less than 0.001). The results suggest that radioimmunoassays of serum conjugated cholic acid and chenodeoxycholic acid in sickle cell disease may also serve as useful biochemical assays in predicting liver dysfunction in sickle cell disease.

Adolescent↗
PubMed2004

Bile-mediated aminoglycoside sensitivity in Lactobacillus species likely results from increased membrane permeability attributable to cholic acid.

Few studies have been conducted on antimicrobial resistance in lactobacilli, presumably because of their nonpathogenic nature as anaerobic commensals. We assessed resistance in 43 type strains and isolates representing 14 species by using agar disk diffusion and MIC analysis in MRS medium. Most noteworthy were two general phenotypes displayed by nearly every strain tested: (i) they were more susceptible (up to 256-fold in some cases) to the deconjugated bile acid cholic acid than to the conjugate taurocholic or taurodeoxycholic acid, and (ii) they became susceptible to aminoglycosides when assayed on agar medium containing 0.5% fractionated bovine bile (ox gall). Two-dimensional MIC analyses of one representative strain, Lactobacillus plantarum WCFS1, at increasing concentrations of ox gall (0 to 30.3 mg/ml) displayed corresponding decreases in resistance to all of the aminoglycosides tested and ethidium bromide. This effect was clinically relevant, with the gentamicin MIC decreasing from >1,000 to 4 mug/ml in just 3.8 mg of ox gall per ml. In uptake studies at pH 6.5, [G-3H]gentamicin accumulation increased over control levels when cells of this strain were exposed to bile acids or reserpine but not when they were exposed to carbonyl cyanide m-chlorophenylhydrazone. The effect was dramatic, particularly with cholic acid, increasing up to 18-fold, whereas only modest increases, 3- and 5-fold, could be achieved with taurocholic acid and ox gall, respectively. Since L. plantarum, particularly strain WCFS1, is known to encode bile salt hydrolase (deconjugation) activity, our data indicate that mainly cholic acid, but not taurocholic acid, effectively permeabilizes the membrane to aminoglycosides. However, at pHs approaching neutral conditions in the intestinal lumen, aminoglycoside resistance due to membrane impermeability may be complemented by a potential efflux mechanism.

Aminoglycosides↗
PubMed1997

Cholic acid synthesis is reduced in pediatric liver recipients during graft dysfunction due to ischemic injury and allograft rejection.

BACKGROUND: Bile acids are synthesized and secreted by the liver. During liver failure and hepatic dysfunction, a marked reduction of bile acid synthesis has been shown. The purpose of this study was to determine whether the biliary bile acid pattern was affected by preservation injury and rejection and whether it was a reliable marker for graft function in pediatric liver recipients after liver transplantation. METHODS: We prospectively measured the biliary bile acid pattern in 126 serial bile samples obtained from 15 consecutive pediatric liver recipients by reversed phase high pressure liquid chromatography and correlated our results with clinical findings: preservation injury, no rejection, rejection, or infection. RESULTS: There was a significant change of the bile acid pattern during the first 3 days after transplant. Total biliary bile acids, cholic acid (CA), and CA/chenodeoxycholic acid (CDCA) ratio increased in 12 of 15 patients with mild preservation injury. These changes of the bile acid pattern were markedly delayed in patients with severe preservation injury. During 16 rejection episodes, total biliary bile acid, CA, and CA/CDCA ratio decreased significantly, but returned to normal after successful treatment of rejection. Bacterial infection, observed in nine children, and cyclosporine toxicity, observed in three children, seemed to have no affect on the biliary bile acids. CONCLUSIONS: Liver cell damage as a result of preservation injury or rejection leads to a reduction of biliary CA, resulting in a decrease of total biliary bile acids and the CA/CDCA ratio in pediatric liver recipients. This might be caused by a diminished secretion of bile acids and by a decreased synthesis of bile acids.

Adolescent↗
PubMed1986

Effects of cholic acid, 7 beta-hydroxy- and 12 beta-hydroxy-isocholic acid on bile flow, lipid secretion and bile acid synthesis in the rat.

The effects of three epimeric trihydroxy-cholanoic acids, cholic acid (C), 7 beta-hydroxy-(7 beta) and 12 beta-hydroxy-(12 beta) isocholic acids on bile flow, lipid secretion, bile synthesis and bile micellar properties were studied in the rat with a bile fistula. The bile salts were infused intraduodenally starting 72 hours after cannulation when endogeneous bile salt synthesis had plateaued after the bile salt pool was drained. The bile salts were infused at two levels approximately 2 and 4 mumol min-1 kg-1. All three bile salts were absorbed and secreted almost quantitatively into the bile. Cholic acid was secreted in the conjugated form, 7 beta conjugated to approximately 60% and 12 beta completely in the unconjugated form. The bile salts did not undergo any significant biotransformations during the one passage from the intestine through the liver. Bile flow increased from the preinfusion level for all three bile salts infused in the order 7 beta greater than 12 beta greater than C. The bile flow increased linearly with bile salt secretion more for 7 beta than for C and 12 beta. Infusion of C increased the secretion into bile of phospholipid (PL) and cholesterol (CH) over the preinfusion values. Infusion of 7 beta as well as 12 beta resulted in a parallel decrease in the secretion of PL as well as CH compared to the preinfusion values. The infusion of C and 7 beta at the two levels used decreased the secretion of newly synthesized bile salt below the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Biosynthesis of cholic acid in rat liver: formation of cholic acid from 3 alpha, 7 alpha, 12 alpha-trihydroxy- and 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acids.

Conversion of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid into 3 alpha, 7 alpha, 12 alpha 24-tetrahydroxy-5 beta-cholestanoic and cholic acids was catalyzed either by the mitochondrial fraction fortified with coenzyme A, ATP, MgCl2 and NAD or by the combination of microsomal fraction and 100,000 x g supernatant fluid fortified with coenzyme A, ATP and nad. 24-hydroxylation and formation of cholic acid occurred at similar rates with the 25R- and the 25S-forms of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid. The 25R- and 25S-forms of 3 alpha, 7 alpha, 12 alpha-trihydroxy- and 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acids were administered to bile fistula rats. Labeled cholic acid was isolated from the bile. The initial specific radioactivity of cholic acid was higher and the disappearance of radioactivity more rapid after administration of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid than of 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid. The findings are discussed in relation to the assumed pathway for side chain cleavage in cholic acid biosynthesis.

Adenosine Triphosphate↗
PubMed1983

Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man.

A multicompartmental pharmacokinetic model based on physiological principles, experimental data, and the standard mathematical principles of compartmental analysis has been constructed that fully describes the metabolism and enterohepatic cycling in man of cholic acid, a major bile acid. The model features compartments and linear transfer coefficients. The compartments are aggregated into nine spaces based on physiological considerations (liver, gallbladder, bile ducts, jejunum, ileum, colon, portal blood sinusoidal blood, and general circulation). The transfer coefficients are also categorized according to function: flow, i.e., emptying of gallbladder or intestinal spaces, and circulation of the blood; biotransformation, i.e., conjugation, deconjugation, or dehydroxylation; and transport, i.e., active or passive transport. The model is made time dependent by introducing meals, which trigger discrete increases in gallbladder emptying and intestinal flow. Each space contains three compartments. For cholic acid, these are unconjugated cholic acid, cholylglycine, and cholyltaurine. The model was then used with all existing experimental data to simulate cholic acid metabolism in healthy man over a 24-h period. Satisfactory agreement was obtained between simulated and experimental results for serum bile acid levels, hepatic bile acid secretion, and bile acid secretion into the intestine. The model was also used to classify 16 clinical instances in which the enterohepatic circulation of bile acids is altered by drugs or disease. The model can be extended to describe completely the metabolism and enterohepatic circulation of any bile acids in man in health and digestive disease. The model should also be broadly applicable to the description of the pharmacokinetics of all other drugs whose metabolism is similar to that of bile acids, i.e., drugs for which there are tissue and bacterial biotransformations, enterohepatic cycling, and appreciable first-pass clearance.

Bile Acids and Salts↗
PubMed1982

The preparation of bile acid amides and oxazolines. II. The synthesis of the amides and oxazolines of ursodeoxycholic acid, deoxycholic acid, hyodeoxycholic acid and cholic acid.

Bile acid amides and oxazolines were synthesized by a sequence of steps involving the reaction of the free bile acid with formic acid to yield the formyloxy derivative, preparation of the formyloxy acid chloride, condensation of the acid chloride with 2-amino-2-methyl-1-propanol to give the amide and, finally, cyclization of the amide with thionyl chloride to give the oxazoline. The oxazolines were characterized by physical constants, thin layer and gas-liquid chromatography and identified by elemental analysis and gas-liquid chromatography-mass spectrometry. Some of the bile acid oxazoline derivatives alter the activity of bacterial 7-dehydroxylases in vitro, and inhibit the growth of certain anaerobic bacteria in pure culture.

Amides↗