Effect of mixed micellar lipid on the absorption of cholesterol and vitamin D3 into lymph

The absorption of endogenous cholesterol, labeled with tracer doses of cholesterol (14)C or cholesterol-(3)H and of near physiological doses of vitamin D(3)-(3)H was studied in rats with cannulated intestinal lymphatics. The effects of administering mixed micellar solutions of fatty acid, monoglyceride, and bile salt on the absorption of these labeled sterols was determined. It was observed that the specific activity of free cholesterol and the amounts of vitamin D(3) appearing in lymph were significantly increased during the intraduodenal administration of mixed micellar solutions of either linoleic or palmitic acid, in contrast to control rats receiving a micellar solution of taurocholate. These increases were related linearly to the lymph triglyceride level. In addition it was observed that when the linoleic acid solution was administered there was a more marked increase in the ratio of the specific activities of free and esterified cholesterol in lymph than with either the palmitic acid or taurocholate solutions.Additional studies in rats with intact lymphatics showed that the uptake of labeled cholesterol and vitamin D(3) from the intestinal lumen into the wall was similar whether the sterols were administered in taurocholate or in mixed micellar solution.These findings suggest that mixed micellar lipid increased the rate of appearance of labeled free cholesterol and vitamin D(3) in lymph by enhancing their transport out of the intestinal mucosa, rather than by an effect on uptake.     

Effect of Neomycin on Cholesterol Metabolism in the Germ-Free Pig

Abstract The effect of neomycin sulphate in an oral dose of 1.5 g daily was studied in germ-free piglets given a preliminary intravenous dose of labelled cholesterol. Combined urinary and faecal pools were assayed for radioactivity and the faecal excretion of neutral sterols and bile acids was calculated by the isotopic balance method. During the administration of neomycin there was only a slight and transient decrease in serum cholesterol, but the faecal excretion of endogenous neutral sterols was more than doubled. There was also a significant rise in faecal fat excretion, although bile acid excretion remained unchanged. Examination of the morphology of the small intestinal mucosa by both light and electron microscopy showed no evidence that neomycin had caused any damage to either absorptive or crypt cells. The only abnormality found was the presence in macrophages in the lamina propria of dense inclusions which exhibited a paracrystalline structure at very high magnification; they were not found in control germ-free animals. These findings demonstrate that neomycin exerts an effect on lipid metabolism which is independent of its antibiotic actions and which is not secondary to mucosal damage.     

Equilibration of labelled and endogenous bile acids in patients with liver cirrhosis after administration of (24-14C)cholic and chenodeoxycholic acids

On separate occasions (24-14C)cholic acid and (24-14C)chenodeoxycholic acid were administered intravenously to patients with liver cirrhosis and the isotope excretion in urine and faeces monitored. Bile acids in serum, urine and faeces were extracted and separated into unconjugated bile acids, glycine- and taurine conjugates, glucuronides and sulphates. Individual bile acid conjugates were separated by high-performance liquid chromatography (HPLC) and the unconjugated bile acids were separated by gas-liquid chromatography (GLC) and identified by gas chromatography-mass spectrometry (GC-MS). Individual bile acid conjugates were quantified and their isotope contents determined. In serum, isotope contents declined rapidly during the first day, followed by a markedly slow rate of reduction. In accordance with this, the excretion of isotope from the patients was found to be very slow and the routes of bile acid excretion were changed, which resulted in an increased ratio of urine/faeces isotope excretion. Studies of the ratio of labelled to endogenous bile acid conjugates indicated that a continuous transformation of the labelled compounds occurred during the period of study. As judged from serum bile acids, conjugation to glycine- or taurine conjugates was rapid. The specific activities of labelled sulphate esters were consistently lower than for other conjugates during the 300-min observation period. During the first day, the urinary bile acids contained a high proportion of unconjugated labelled bile acids, which gradually disappeared. Labelled primary bile acids were slowly converted into microbial products, mainly 7-alpha dehydroxylated derivatives. The observed slow transformations resulted in a much delayed equilibration of labelled and endogenous bile acid derivatives, which invalidates isotope techniques for calculation of kinetic data of bile acid turnover. However, the observed very slow turnover of labelled bile acids in cirrhosis, owing to the persistent high rate of intestinal absorption and low capacity for urinary excretion, makes it possible for the intestinal flora to markedly change the composition of the bile acids in the pool. Studies of endogenous urinary and faecal bile acid excretion revealed the changed route of bile acid excretion with a high urinary/faeces ratio and the decreased synthesis of bile acids in cirrhosis.     

Bile salt regulation of fatty acid absorption and esterification in rat everted jejunal sacs in vitro and into thoracic duct lymph in vivo

This study was performed to investigate whether the malabsorption of fat in the blind loop syndrome is due to the presence of free bile acids or to a deficiency of conjugated bile salts produced by bacterial degradation of normal bile salts, as well as to learn something of the mechanisms by which bile salts might regulate fat absorption. In the everted gut sac of the rat in vitro, conjugated bile salts were necessary for maximal rates of fatty acid esterification to triglycerides, whereas free bile acids inhibited this process even in the presence of physiologically normal or higher concentrations of conjugated bile salts. In contrast, in the living animal the addition of similar or higher concentrations of free bile acids to infusions of fatty acids in taurocholate micellar solutions produced no reduction in the amount of fatty acid absorbed into lymph or the amount of fatty acid esterified into lymph triglyceride. Both in vitro and in the living animal, reduction in the conjugated bile salt concentration reduced both the rate of fatty acid uptake by the intestine and the esterification into triglycerides. It is concluded that the steatorrhea of the blind loop syndrome or other conditions in which upper intestinal stasis allows bacterial proliferation is not due to presence of increased gut luminal concentrations of free bile acids, but rather is a consequence of lowered concentrations of conjugated bile salts.     

Relationship between Faecal Bile Acids, Absorption of Fat and Vitamin B12, and Serum Lipids in Patients with Ileal Resections

Abstract. Faecal bile salt, neutral steroid and fat excretion, vitamin B₁₂ absorption, and jejunal lipids, bile acids and cholesterol during fat digestion, serum cholesterol and cholesterol synthesis were measured in 3 patients with incomplete (IIR) and 9 patients with complete (CIR) resection of the terminal ileum. These parameters were virtually normal in IIR and in one case with CIR while in other cases they were frequently abnormal, bile salt excretion being increased up to 12-fold. The finding that faecal bile salts correlated positively with faecal fat and cholesterol synthesis, and negatively with jejunal constituents and serum cholesterol, supports the previously unproved concept that augmented elimination of cholesterol into faeces as bile acids proportionately depletes serum cholesterol despite increased cholesterol synthesis, proportionately decreases jejunal bile salts despite markedly augmented bile acid production and proportionately impairs micellar solubilization of lipids during fat absorption, leading to steatorrhoea. Furthermore, faecal bile salts showed a positive correlation with faecal water and a negative one with the Schilling test values. Faecal bile salts are suggested to be a sensitive indicator of ileal dysfunction.     

Absorption of oleic and palmitic acids from emulsions and micellar solutions

A lipid mixture (monoolein, oleic acid-1-(14)C, and palmitic acid-9,10-(3)H) was infused intraduodenally at a steady rate for 8 hr in fasted, unanesthetized rats. The same dose of lipid was given together with pure conjugated bile salts either as an emulsion, 2.5 mM bile salts, or as a micellar solution, 10 mM bile salts. The emulsion contained very little or no micellar lipid. Thoracic duct lymph was collected and in some experiments bile and pancreatic juice were drained to the exterior. After 4-5 hr infusion the same steady lymphatic output of radioactive fatty acids was obtained with emulsion as with micellar solution. It was concluded that absorption of fatty acid could proceed efficiently in the virtual absence of micellar solubilization. In rats with biliary plus pancreatic fistulae, labeled triglyceride was absorbed poorly relative to free fatty acids in the same emulsified particles. This suggested that fatty acids were transferred to the absorptive cells in monomolecular solution and not as emulsion particles.Substitution of a synthetic nonionic detergent for bile salts in lipid mixtures given to rats with biliary and pancreatic fistulae did not affect the lymphatic output of radioactive fatty acids. This indicated that mucosal esterification of labeled free fatty acids was normal in the absence of bile salts. The physical state of the lipid did not affect the pathway of absorption. Finally, comparison of the increased output of esterified fat in the lymph with the output of labeled fat suggested that fat absorption did not greatly affect the turnover of endogenous, unlabeled fat. Results were consistent with the view that most of the endogenous lymph fat comes from reabsorbed biliary lipid.     

Action of neomycin on the intraluminal phase of lipid absorption

Administration of a single 1 g dose of neomycin sulfate to five healthy subjects simultaneously with a test meal caused a marked increase in the proportion of fatty acid and bile acid in the ultracentrifuged deposit of aspirated intestinal contents. Labeled cholesterol was precipitated in a similar manner in two hypercholesterolemic patients. Neomycin had no effect on the pancreatic lipase concentration or on the pH of intestinal contents. These results confirm that the ability of neomycin to precipitate micellar lipids is due to interaction between the polybasic neomycin molecule and ionized fatty acids and bile acids. This mechanism provides an explanation for both the steatorrhea and hypocholesterolemia induced by this compound.     

Cholesterol reduces the effects of dihydroxy bile acids and fatty acids on water and solute transport in the human jejunum.

Jejunal perfusion studies were performed in 16 healthy volunteers to test the hypothesis that intraluminal cholesterol can mitigate the fluid secretion induced by dihydroxy bile acids and fatty acids. Fluid secretion in the presence of 5 mM taurodeoxycholate was somewhat reduced by 4 mM mono-olein which was used for the solubilization of cholesterol. Addition of 0.8 mM cholesterol reduced fluid secretion further (P less than 0.05). Fluid secretion induced by 4 mM oleic acid was changed to net absorption in a linear fashion with increasing cholesterol concentration in the perfusion solutions. 1 mM cholesterol reduced fluid secretion induced by 6 mM oleic acid (P less than 0.005), but had no effect on fluid secretion induced by 6 mM linolenic acid. Glucose absorption was generally affected in a similar manner as water transport. In vitro, 1 mM cholesterol reduced monomer activity of 6 mM oleic acid to 72.3 +/- 0.9% of control and that of linolenic acid to 81.1 +/- 1.7% of control. Although statistically significant (P less than 0.001), the difference in the effects of cholesterol on monomer activities of the two fatty acids was rather small and it is unlikely that changes in monomer concentration of fatty acids and bile acids account for the protective effect of cholesterol. The in vivo observations point to a new physiological role for biliary cholesterol: the modification of the response of the small intestine to the effects of dihydroxy bile acids and fatty acids.     

Lipid metabolism in bile acid malabsorption

Malabsorption of bile acid increases cholesterol synthesis and activates hepatic LDL receptors which leads to enhanced elimination of cholesterol from the body. Interruption of enterohepatic circulation of bile acids may lead to a smaller bile acid pool, which, in turn, impairs cholesterol and fat absorption by reduced micellar solubilization. Together with reduced cholesterol absorption, the increased cholesterol loss as bile acids also reduces plasma cholesterol concentrations and the biliary cholesterol excretion, too. Diminished biliary cholesterol in bile acid malabsorption may contribute to the increased incidence of gallstones associated with ileal dysfunction. Malabsorption of bile acid leads to a fall in LDL-cholesterol concentration, and an increase of HDL-cholesterol concentration has been reported. VLDL-triglyceride concentrations are almost invariably raised. Enhanced cholesterol and bile acid synthesis in ileal dysfunction is reflected by raised concentrations of plasma cholesterol precursors, especially lathosterols, which can be used as an indicator of increased bile acid loss to faeces. Cholesterol absorption, in turn, correlates positively with plasma plant sterol concentrations levels and the ratio of lathosterols to campesterols can be used as a screening measurement for ileal dysfunction. Plasma fatty acid composition is also altered as a response to fat malabsorption associated with ileal dysfunction. The proportion of essential fatty acids is inversely correlated with faecal fat excretion and endogenous fatty acid synthesis is activated.     

Effects of dihydroxy bile acids and hydroxy fatty acids on the absorption of oleic acid in the human jejunum.

Perfusion studies of the normal human jejunum were performed to test whether dihydroxy bile acids and hydroxy fatty acids inhibit the absorption of oleic acid, since previous reports documented their inhibitory effects on the absorption of several other organic solutes. 3 mM deoxycholate and 7 mM glycodeoxycholate inhibited the absorption of 3 mM oleic acid in isotonic micellar solutions while inducing net fluid secretion. Similarly, fractional absorption of oleic acid decreased in the presence of hydroxy fatty acids. However, only the changes induced by 2 mM ricinoleic acid could be distinguished from changes induced by an increase in total fatty acid concentration. Under all experimental conditions, close linear relationships existed between net water movement and fractional absorption of glucose, xylose, and fatty acids, as well as between the absorption rates of these solutes. In contrast, net fluid secretion induced by hypertonic D-mannitol (450 mosmol/liter) had no effect on solute absorption. Our data and observations in the literature do not allow formulation of a hypothesis which would adequately define all effects of dihydroxy bile acids and fatty acids on intestinal transport processes. The observations help explain the malabsorption of fat and other nutrients in patients with the blind loop syndrome.     

Characterization of Bile Acid Absorption across the Unstirred Water Layer and Brush Border of the Rat Jejunum

We have examined the rate-limiting steps involved in bile acid absorption across the unstirred water layer and lipid cell membrane of the jejunal mucosa. Uptake of the polar bile acid taurocholate is limited solely by the cell membrane since this compound permeates the unstirred water layer more rapidly than the lipid cell membrane and stirring does not enhance uptake. With less polar bile acids which permeate the cell membrane relatively more rapidly, however, the unstirred water layer does exert resistance to mucosal uptake of these compounds. That the unstirred water layer is even more rate limiting to uptake from micellar solutions is indicated by the facts that the rate of bile acid absorption from such solutions is lower than from corresponding monomer solutions, stirring markedly enhances uptake from micellar solutions while increases in viscosity of the incubation media depress uptake and expansion of the micelle size further depresses absorption rates. We also have examined the important question of whether the micelle crosses the brush border intact once it reaches the aqueous-lipid interface. The observations that the calculated permeation rate of the micelle should be extremely low, the rate of mucosal cell uptake plateaus at a constant value when the critical micelle concentration is reached at the aqueous-lipid interface, and the different components of a mixed micelle are taken up at different rates indicate that uptake of the intact micelle does not occur; rather, bile acid absorption must be explained in terms of monomers in equilibrium with the micelle. Finally, after correction of the permeability coefficients of the various bile acids for the unstirred layer resistance the incremental partial molar free energy of solution of the hydroxyl group in the brush border membrane was calculated to equal -6126 cal.mole(-1) indicating that passive diffusion of these compounds occurs through a very polar region of the cell membrane.     

The measurement of sulphated and non-sulphated bile acids in serum using gas-liquid chromatography.

A method is described to assay sulphated and non-sulphated bile acids in serum using gas-liquid chromatography. Previously described techniques have been substantially modified to allow analysis of free and conjugated salts of the four major bile acids with particular care to ensure quantitative recoveries of lithocholic acid, its conjugates and sulphate esters. Losses of lithocholic acid inherent in some methods have been reduced by avoidance of column chromatography with alumina and extraction of lipid contaminants into heptane. Assay of the proportion of serum bile acids present as sulphate esters is achieved by the routine use of column chromatography to separate sulphated bile acids from non-sulphated bile acids followed by solvolysis of the sulphated bile acids before deconjugation. Careful selection of the conditions of strong alkaline hydrolysis ensures deconjugation of all bile salt conjugates including lithocholic conjugates which are not completely hydrolysed in weaker alkaline solutions. The trifluoroacetate derivatives of the methyl esters of the bile acids are chromatographed using 5-beta-cholanic acid as an internal standard with clear separation of the four major bile acids from the internal standard. In 10 fasting control subjects the mean serum total bile acid concentration was 5.3 muM (RANGE 1.1-16.4) including 0.7 mum sulphated bile acid (range 0-1.8). In 10 patients with acute viral hepatitis the total bile acid concentration was elevated in some but normal in others (mean 44.9 muM, range 2.7-80.3). The percentage of the total bile acid sulphated was not significantly different in the hepatitis patients compared to controls (controls 13%, range 0-35; hepatitis 23%, range 0-52). Lithocholic acid made up 13% of the total bile acid in controls (0-32%) and 18% in hepatitis patients (0-53%). Most of this lithocholic acid was sulphated (controls 81%, range 30-100; hepatitis 67%, range 37-100). Unconjugated bile acids were demonstrated in the serum of a few patients with acute viral hepatitis but in no control subjects.     

Isolation and properties of the mixed lipid micelles present in intestinal content during fat digestion in man.

To evaluate better the physicochemical characteristics of human fat digestion, a method was developed which allowed characterization of the bile acid-lipid mixed micelles of the aqueous phase of post-prandial duodenal fluid. Duodenal fluid was collected after a 36-g fat breakfast for two 90-min periods and for 60 min after i.v. cholecystokinin and was ultracentrifuged at 15,400,000 g-min. The aqueous phase was isolated, passed through a 200-nm filter, and the mixed micelles were concentrated by an ultrafiltration procedure using a 1.5-nm filter. The 1.5-nm retentate was eluted from Sepharose 6B columns with 1.5-nm filtrate for both preequilibration fluid and eluent. 1.5-nm filtrate approximated the monomer concentrations. Each sample was assayed for bile acid, fatty acid, lecithin, lysolecithin, protein, cholesterol, and counterions (pH, Na+, K+, Ca2+). Constituents were concentrated only on the 1.5-nm filter. On gel permeation chromatography, coincident peaks were observed for bile acid, fatty acid, lysolecithin, and cholesterol; and were eluted with a Kav range of 0.50-0.68 (corresponding to a Stokes radius of 2.3-3.5 nm). An average density of 1.25 and coincident peaks of bile acid and fatty acid were found for the mixed micelles on sucrose density gradients. The regression lines of micellar fatty acid, lysolecithin, and cholesterol vs. bile acid gave a stoichiometry of 1.4 mol fatty acid, 0.15 mol lysolecithin, and 0.06 mol cholesterol for each mole of bile acid. Mixed micelles were homogeneous in composition. These results provide direct evidence for the existence of the postprandial mixed micelle and describe several of its physicochemical properties.     

Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic cycling of bilirubin in hamsters

BACKGROUND: We have evidence for enterohepatic cycling of bilirubin experimentally and in vivo in humans. This study was designed to investigate whether Zn salts might inhibit such cycling of bilirubin. MATERIALS AND METHODS: Micellar bile salt solutions with unconjugated bilirubin were prepared, appropriate concentrations of Zn salts were added, and unconjugated bilirubin precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored. RESULTS: Unconjugated bilirubin was precipitated maximally (90%) after a 10-min incubation with 5 mM Zn salts in the pH range of 6.8-9.0. In control hamsters, total bilirubin secretion rates into bile were 36.0 +/- 2.8 nmol h(-1) 100g(-1) body weight, whereas they were 25.0 +/- 3.3 nmol h-1 100(-1) g in the ZnSO4 group (P < 0.05). CONCLUSIONS: Zn salts that flocculate at physiological pH adsorb unconjugated bilirubin almost completely from unsaturated micellar BS solutions. In addition, Zn salts administered orally suppress biliary bilirubin secretion rates in hamsters. These findings suggest that the administration of Zn salts may inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are predisposed to pigment gallstone formation due to diet, disease or drugs.     

Studies on the pathogenesis of diet-induced dog gallstones.

Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.     

Effect of cholestyramine on bile acid pattern and synthesis during administration of ursodeoxycholic acid in man

BACKGROUND: Cholestyramine is the first-line treatment for cholestasis-induced pruritus and is prescribed along with ursodeoxycholic acid (UDCA) in patients with cholestatic liver diseases. Impairment of the intestinal absorption of endogenous hydrophobic bile acids by cholestyramine is well known. It is unclear, however, whether cholestyramine also impairs the absorption of the hydrophilic bile acid, UDCA, in man. AIMS: To study serum levels of UDCA and endogenous bile acids as well as endogenous bile acid synthesis during simultaneous or separate administration of UDCA and cholestyramine in vivo; and absorption of UDCA both in the presence and absence of its hydrophobic epimer, chenodeoxycholic acid (CDCA), by cholestyramine in vitro. PATIENTS AND METHODS: Five healthy subjects received UDCA (12.5 +/- 0.5 mg kg-1 daily) as a single dose for periods of 14 days with or without cholestyramine (4 g daily). Fasting serum levels of bile acids and of 7alpha-hydroxy-4-cholesten-3-one (alpha-HC), a measure of endogenous bile acid synthesis, were determined by gas chromatography and high pressure liquid chromatography, respectively. In vitro, bile acid solutions were incubated for 24 h in the presence or absence of cholestyramine, and bile acid concentrations were determined in the supernatant. RESULTS: Simultaneous administration of UDCA and cholestyramine in man led to a decrease of fasting serum levels of UDCA by 60% when compared to UDCA serum levels during administration of UDCA alone. In contrast, serum levels of endogenous bile acids were not affected and alpha-HC serum levels were found increased 2. 7-fold indicating stimulation of endogenous bile acid synthesis by cholestyramine. Administration of cholestyramine and UDCA at an interval of 5 h tended to diminish the effect of cholestyramine on UDCA serum levels. In vitro, conjugated and unconjugated UDCA were effectively bound by cholestyramine both in the presence and absence of hydrophobic bile acids. CONCLUSIONS: The results strongly support the recommendation to administer UDCA and cholestyramine at different times of day.     

Effects of feeding ursocholic acid to germfree rats

Germfree rats were fed 24-14C-ursocholic acid (UC) mixed into the diets for 10 days. The bile was then drained by cannulation for 6 hours to collect the bile salt pool. No biotransformation of the labelled UC occurred and it constituted approximately equal to 75% of an enlarged bile salt pool. Less phospholipid and cholesterol were secreted into the bile per mumol bile salt compared to normal rats. The critical micellar concentration (CMC) of the bile was determined by equilibrium dialysis and found to be increased. Faecal excretion of labelled triolein added to the diet was unaffected by feeding ursocholic acid. Excretion of 14C-octadecane and 14C-cholesterol increased significantly under the same conditions. Ursocholic acid feeding thus resulted in a selective malabsorption of octadecane and cholesterol.     

Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate

BACKGROUND: Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. METHODS: We studied absorption and biliary bile acid secretion and composition after administration of UDCA and TUDCA in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but had no intestinal or liver disease. After 5 days of intact enterohepatic circulation eight patients with a percutaneous biliary-duodenal drainage received, during two study periods, 1000 mg (1916.9 micromol; mean 29.6 micromol kg(-1)) TUDCA and 750 mg (1910.4 micromol; mean 29.5 micromol kg(-1)) UDCA in random order. Each patient served as his own control. RESULTS: After UDCA and TUDCA administration the biliary UDCA content increased to 55.2% and 54.6% of total bile acids, respectively (not significant). Biliary secretion of cholic and chenodeoxycholic acids remained unchanged whereas that of lithocholic acid increased slightly. A total of 64.6% of the orally administered TUDCA and 55.1% of the UDCA was absorbed (not significant). After TUDCA administration, biliary UDCA was preferentially (95.4%) taurine-conjugated whereas after UDCA administration biliary UDCA was mainly (79.8%) glycine-conjugated. CONCLUSIONS: After oral administration of TUDCA and UDCA, no significant differences in their absorption and in biliary bile acid secretion exist. Whether biliary enrichment with taurine conjugates of UDCA instead of glycine conjugates offers advantages in the treatment of cholestatic liver disease is unclear at present.     

Lipid composition of bile in morbid obesity before and after jejunoileal bypass surgery

Bile cholesterol, phospholipids, total bile acids, individual bile acids, and fatty acid compositions of bile neutral lipids and phospholipids were analyzed before, at one month and at six months following jejunoileal bypass surgery in a series of morbidly obese patients. Preoperative mole percentages of cholesterol and lithogenic indices were high, indicating that biles were supersaturated with cholesterol and outside the micellar solubility zone when plotted on triangular coordinates. At the one month post-operative period percentages of cholesterol and lithogenic indices were significantly increased as compared to the pre-operative state. At six months post-operatively these values had decreased to approximately the pre-operative levels. No changes were observed in percentages of lithocholic acid, but deoxycholic acid decreased to markedly low levels at one month and remained low at the six month post-operative interval. Relative proportions of cholic acid increased, and the ratio of cholic to chenodeoxycholic acid was significantly increased at both post-operative intervals. No significant changes were noted in bile neutral lipid or phospholipid fatty acid composition, indicating that no depletion of essential fatty acids had occurred.     

Premicellar taurocholate avidly binds ferrous (Fe++) iron: a potential physiologic role for bile salts in iron absorption

Two of the major divalent cations in human physiology, Ca++ and Fe++, are poorly soluble at the pH of intestinal contents, and active "uphill" transport mechanisms exist for both ions in proximal small intestine. We have recently demonstrated significant binding of Ca++ to both premicellar and micellar bile salts and have postulated that high-affinity premicellar binding involves interposition of Ca++ between terminal carboxyl (COO-) and 7-OH or 12-OH groups of the steroid ring. The present studies were made to determine whether such binding extends to other divalent cations, and specifically to Fe++, which, like Ca++, has a hydrated diameter of 6 A. Equilibrium dialysis studies of sodium taurocholate were made at 25 degrees C with solutions containing 0.5 to 150 mmol/L taurocholate and 0.018 to 1.8 mmol/L iron 59-labeled FeSO4 at pH 3.0 to 6.3 and a total ionic strength of 0.15 mol/L. In control (saline dialysand) cells, [Fe++] was virtually equal in dialysands and dialysates within 5 hours. In sharp contrast, taurocholate-containing dialysands showed significantly higher counts than dialysates, indicating Fe++ binding to taurocholate, independent of pH and Fe concentration. After correction for taurocholate-induced Gibbs-Donnan effects across the membrane, the apparent taurocholate affinity constant (K'f) for Fe++ in micellar solutions (5 to 150 mmol/L) was essentially constant at about 3.1 (mol/L)-1, then increased dramatically below the critical micellar concentration to greater than 100 (mol/L)-1 at [taurocholate] = 0.5 mmol/L. The hyperbolic rise in K'f below the critical micellar concentration is similar to that which we have previously reported for Ca++, indicating significant high-affinity binding of Fe++ to premicellar taurocholate anions and low-affinity binding to micellar anions. It is postulated that Fe++ binding, particularly by premicellar bile salts, may play an important physiologic role in increasing iron solubility within the intestinal lumen, thus increasing iron absorption. The possible role of bile salts in increasing divalent cation solubility and absorption from the intestine is a new field of bile acid research.