EFFECTS OF ADRENALECTOMY AND CORTICOID REPLACEMENT ON BILE ACID CONJUGATION IN BILE FISTULA RATS

1963 ◽  
Vol 43 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Kjell Hellström ◽  
Ove Strand

ABSTRACT Bile fistula bile from male normal, sham-operated, adrenalectomized and cortisone substituted adrenalectomized rats was analyzed for free and conjugated bile acids. 40–50 per cent of the bile acids from adrenalectomized rats were conjugated with glycine as compared to less than 10 per cent in the other groups. The cortisone substituted adrenalectomized rats showed a lower glycine conjugation than normal rats. In the bile from adrenal-ectomized rats, free cholic acid corresponding to 2–5% of the conjugated bile acids was detected. In the bile from the other groups less than 1% of free cholic acid was found. The mechanism responsible for the abnormal conjugation pattern found in adrenalectomized rats is discussed.

1982 ◽  
Vol 242 (1) ◽  
pp. G40-G46 ◽  
Author(s):  
I. T. Gilmore ◽  
J. L. Barnhart ◽  
A. F. Hofmann ◽  
S. Erlinger

The effect of three taurine-conjugated bile acids on bile flow, induced biliary secretion of phospholipids and cholesterol, and the hepatobiliary clearance from plasma of sucrose and erythritol (two uncharged, nonmetabolizable permeability probe molecules) was assessed in the unanesthetized bile fistula dog under steady-state conditions. Synthetically prepared chenodeoxycholyltaurine, cholytaurine, or urological rate for randomized 90-min periods, and four 10-min samples of bile were taken at the end of each period. Induced bile flow (per mumoles of bile acid) was calculated to be about one-third higher with ursodeoxycholyltaurine than with the other bile acids. Induced phospholipid secretion was identical for all bile acids, but cholesterol secretion differed: the two dihydroxy taurine conjugates induced considerably more cholesterol per molecule bile acid or phospholipid than colyltaurine. Further, ursodeoxycholyltaurine induced significantly more cholesterol secretion than chenodeoxycholyltaurine. Erythritol clearances were identical for all bile acids, and sucrose clearance, although slightly higher for chenodeoxycholyltaurine than ursodeoxycholyltaurine, was similar for all three conjugated bile acids. The results indicate that, for these two 3,7-dihydroxy bile acids, the orientation of the 7-hydroxyl group on the steroid nucleus has a marked influence on cholesterol secretion into bile and bile flow but not on the apparent permeability of the hepatobiliary tree.


1973 ◽  
Vol 45 (2) ◽  
pp. 147-161 ◽  
Author(s):  
M. D. Kaye ◽  
J. E. Struthers ◽  
J. S. Tidball ◽  
Elizabeth DeNiro ◽  
F. Kern

1. Clearance of [14C]cholic acid from the systemic circulation was studied in six normal subjects and eight patients with biopsy-proven hepatic cirrhosis. In both groups, during fasting, the curve for disappearance of radioactivity from the serum during the first 100 min after [14C]cholic acid injection was double-exponential in form. During the early phase, clearance was significantly more rapid, and concentrations of conjugated and free bile acid were significantly lower, in normals than in cirrhotics. 2. Radioactivity disappeared from the systemic circulation of normals within 3 h, and neither intravenous cholecystokinin nor the ingestion of food influenced serum radioactivity. Almost all cirrhotic patients had ‘spontaneous’ rises in serum radioactivity, which began approximately 2 h after [14C]cholic acid injection. Cholecystokinin or food given 4–8 h after [14C]cholic acid administration, produced rises. Continuous aspiration of duodenal juice markedly reduced these rises. Reinfusion of duodenal juice into the upper intestine was followed by a rise in serum radioactivity. 3. All rises were due, almost exclusively, to conjugated bile acids. 4. Impaired bile acid clearance in cirrhotics may result from inefficient hepatic extraction of bile acids, increased leakage of conjugated bile acids from hepatic cells and shunting from portal to systemic circulations. The latter factor is probably responsible for elevated, fluctuating, plasma bile acid concentrations in cirrhotic patients.


1989 ◽  
Vol 62 (3) ◽  
pp. 539-550 ◽  
Author(s):  
T. Ide ◽  
M. Horii ◽  
K. Kawashima ◽  
T. Yamamoto

A relationship between bile acid conjugation and hepatic taurine concentration was investigated in rats fed on citrus pectin. When rats were fed on the diets containing varying amounts of pectin (10, 30, 60 and 100 g/kg dietary levels), biliary excretion of bile acids increased as the dietary levels of pectin increased. The increase was entirely due to the glycine-conjugated bile acids. The biliary excretion of taurine-conjugated bile acid was somewhat decreased as the dietary level of the fibre increased. Consequently, most of the bile acids were conjugated with glycine in rats fed on the diet containing 100 g pectin/kg. On the other hand, dietary cellulose (60 and 100 g/kg) did not affect the biliary bile acid excretions. The major proportion of bile acids in rats receiving a fibre-free diet and the diets containing cellulose were conjugated with taurine. Hepatic taurine concentrations decreased as the dietary levels of pectin, but not of cellulose, increased. Although dietary pectin (100 g/kg) also slightly decreased the taurine concentration in the kidney, those concentrations in other non-hepatic tissues examined (heart, brain and serum) were unaffected by the dietary fibre. Supplementation of the diet containing 100 g pectin/kg with methionine (10 g/kg) and taurine (10 and 50 g/kg) strikingly increased hepatic taurine concentrations. In this situation, the conjugation of bile acid with glycine was almost abolished and taurine conjugates became abundant in the bile of these animals. It is suggested that dietary pectin mediated an increase in the biliary bile acid excretion which may have depleted the hepatic pool of taurine available for bile acid conjugation and, thus, increased glycine conjugation of bile acids.


1978 ◽  
Vol 16 (18) ◽  
pp. 69-71

Chenodeoxycholic acid (CDCA) (Chendol - Weddel) is one of two naturally occurring ‘primary’ bile acids (the other being cholic acid) made in the liver from cholesterol. CDCA is synthesised commercially from cholic acid and prescribed as gelatin-coated capsules containing 125 mg CDCA.


1979 ◽  
Vol 25 (2) ◽  
pp. 264-268 ◽  
Author(s):  
O Mäentausta ◽  
O Jänne

Abstract We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). Before radioimmunoassay, 0.1-mL serum samples were precipitated with nine volumes of ethanol, and portions from the supernate were used in the assays. The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates. 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 3.2 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +/- SD) of the bile acid conjugates in serum from apparently healthy women and men (in mumol/L) were: cholic acid conjugates, 0.43 +/- 0.17 (n = 126); chenodeoxycholic acid conjugates, 0.47 +/- 0.23 (n = 111); and deoxycholic acid conjugates, 0.33 +/- 0.11 (n = 96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases.


1983 ◽  
Vol 29 (12) ◽  
pp. 1653-1660 ◽  
Author(s):  
Toshichika Ohtomo

In a previous paper, we showed that bile acid derivatives inhibit capsule formation as well as taurine biosynthesis in a taurine+ (Tau+) encapsulated strain of Staphylococcus aureus. In the present study, binding of [14C]cholic acid ([14C]CA) and [14C]taurocholic acid ([14C]TA) to the staphylococcal polysaccharide antigen (SPA) of the capsular fraction was examined. The bile acids were found to bind with SPA via taurine of the Tau+ cells. [14C]CA bound with the SPA fraction of the Tau+ strain within 10–30 min, whereas 60–120 min was required in the binding of [14C]TA. Various bile acids competed with cholic acid binding to Tau+ cells which was shown by the inhibition of binding with cholic acid or taurocholic acid but not with glycholic acid. Binding of bile acid derivatives to a Tau− encapsulated mutant or to capsular material from this mutant was not observed.


2017 ◽  
Vol 35 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Davor Slijepcevic ◽  
Stan F.J. van de Graaf

Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.


2018 ◽  
Vol 84 (10) ◽  
Author(s):  
Heidi Doden ◽  
Lina A. Sallam ◽  
Saravanan Devendran ◽  
Lindsey Ly ◽  
Greta Doden ◽  
...  

ABSTRACTBile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacteriumClostridium leptum; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such asClostridium scindens,Clostridium hylemonae, andClostridium hiranonis. Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread amongFirmicutes,Actinobacteriain theCoriobacteriaceaefamily, and human gutArchaea.IMPORTANCE12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteriaC. scindens,C. hiranonis, andC. hylemonae. Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract.


1973 ◽  
Vol 45 (3) ◽  
pp. 403-406
Author(s):  
R. A. Smallwood ◽  
P. Jablonski ◽  
J. McK. Watts

1. [14C]Cholesterol was administered intravenously via the umbilical vein to foetal sheep in the latter half of gestation, and the incorporation of radioactive label into foetal bile acids was assessed. 2. After 4 days, 0·5–2% of the radioactive label was found in foetal bile. Seventy to eighty per cent of the radioactive label in foetal bile was present as [14C]taurocholic acid and [14C]taurochenodeoxycholic acid. The remainder was [14C]cholesterol. No radioactive label was found in taurodeoxycholic acid, or in any of the glycine-conjugated bile acids. 3. It is concluded that the foetal sheep liver in the second half of gestation synthesizes taurocholic acid and taurochenodeoxycholic acid. However, the secondary bile acid taurodeoxycholic acid and the glycine-conjugated bile acids, present in foetal bile, have been acquired by placental transfer from the mother.


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