Taurocholate enterohepatic circulation

Fig. 5. Transport of bile acids in the enterohepatic circulation. The left and right sides of the figure depict a liver and intestinal cell, respectively. Bile acids (BA) are made from unesterified cholesterol (UC) in the liver. The movement of bile acids in the enterohepatic circulation is vectorial. The major transporters thought to be responsible for the entry and exit of bile acids in liver and intestinal cells are sodium/taurocholate cotransporting polypeptide (ntcp SLClOAl), bile salt export pump (bsep ABCBll), apical/sodium bile acid cotransporter (asbt SLC10A2), and organic solute transporters a/p, (Osta/P).

The enterohepatic circulation of bile salts involves the cycling of fairly large quantities of material. It has been estimated that the human liver secretes some 30 g of bile salts per day. Of these 30 g, approximately 0.8 g per day is newly synthesized material (4). This emphasizes the efficiency of the intestinal reabsorptive processes. The liver also is remarkably efficient in extracting bile salts from portal blood, as evidenced by the fact that the concentration of bile salts in peripheral plasma is a small fraction of that of portal plasma (5-7). Direct determination of taurocholate and glycocholate extraction by the liver in the dog has been measured by O Maille et al. (8) and found to be 92%. 

Fig. 6. Rate of disappearance of sodium taurocholate-24-from the enterohepatic circulation 24, 48, and 72 hr after intravenous injection into a patient with Whipple s disease before and 3 months after treatment with antibiotics (left panel). Composition of residual radioactivity in duodenal fluid obtained at 3, 24, 48, and 72 hr after the intravenous injection of sodium taurocholate-24-i C into patient E. C. with Whipple s disease before and 3 months after antibiotic treatment (right panel). Data are expressed in terms of percentage of radioactivity contributed by each bile salt fraction to the total recoverable i C radioactivity. GDC, glycodeoxycholate GC, glyco-cholate TDC, taurodeoxycholate TC, taurocholate. In part from Garbutt et al. (9).

Studies with radioactive glycocholate or taurocholate demonstrated a virtual absence of the enterohepatic circulation of bile acids in patients with jejunotransversocolostomy (77). The small amount of absorbed bile acids contained some deconjugated cholate and deoxycholate (which had been reconjugated in the liver), indicating a rapid bacterial action during an apparently fast intestinal passage. Under these conditions, steatorrhea is apparently not solely due to bile salt deficiency induced impairment of micelle formation, but reduced absorptive area may play an important contributory role. No direct measurement of bile acid synthesis by fecal determination has been performed in this condition. 

Two primary bile acids are synthesized in the liver from cholesterol. These are cholic acid and chenodeoxycholic acid. They are conjugated with the amino acids, glycine and taurine, to form bile salts (for example taurine may be conjugated with cholic acid to give taurocholic acid). The bile salts are excreted in the bile, and in the gut they are acted upon by bacteria which convert them to the secondary bile acids, deoxycholic acid and lithocholic acid. Some of the secondary bile acids are absorbed and carried by the enterohepatic circulation to the liver where they are re-excreted. 

Several lines of evidence suggest that, in addition to a requirement for an intact enterohepatic circulation of,bile, cholesterol absorption is dependent on the chemical nature of the luminal bile acid. In acute studies on the absorption of cholesterol in thoracic duct lymph of rats, a quantitative relationship between administered cholesterol, fatty acids and sodium taurocholate was... 

It has been shown that simultaneous infusion of taurocholic acid overcomes the cholestatic effect of lithocholic and taurolithocholic acid[2,32,33], possibly by micellar solubilization of the toxic molecules and promotion of their excretion into bile. Therefore, in situations that are characterized by low biliary bile acid output rates, the liver may be more susceptible to the hepatoxic action of monohydroxy bile acids. We studied the effects of endogenous bile acids on the cholestatic action of SGLC in rats. For this purpose we used an animal model in which the enterohepatic circulation (EHC) can be interrupted and restored without direct surgical intervention. 

A review by Heaton and Morris [221] recalls the development of ideas about bile salts and "bitter humour. The enterohepatic circulation of the bile salts was an early discovery the site of absorption of the bile salts in the intestine was a later topic of study. Absorption by the jejunum of sodium taurocholate is negligible both below and above the CMC and it was absorbed mostly in the ileum [222]. It has been established that bile salts are absorbed by an active transport process, absorption being related to the number of hydroxyl groups on the molecule. 

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