Taurolithocholic acid

Dahlstrom-King L, Couture J, Plaa GL. 1992. Influence of agents affecting monoxygenase activity on taurolithocholic acid-induced cholestasis. Toxicol Lett 63 243-252. 

Pancreas (mouse freshly isolated Taurolithocholic acid 71... 

TLCA taurolithocholic acid, TUDCA tauroursodeoxycholic acid... 

Bile acids have historically received much less attention than other steroids, for example the corticosteroids however, now that useful thertqreutic effects ate being observed from some bile acids, there is fresh interest in Ais area. A strain of Cunninghamella Uakesleeana has been isolated that will 15p-hy-droxylate lithocholic acid (80 equation 26) in 31% yield.Further reaction is possible to give 3a,lip,15p-trihydroxy-5p-cholanic acid (15%), 3a,15p,18a-trihydioxy-5p-cholanic acid (4%) and 3a,lla,15p-trihydroxycholanic acid (9%). Taurolithocholic acid (81 equation 27) can be 7p-hydroxy-lated in virtually quantitative yield by Mortierella ramanniana. ... 

Synthesis of sulphate esters of14COOH-lithocholic and taurolithocholic acids... 

Palmer (133) has isolated labeled glycolithocholic acid 3-sulfate and taurolithocholic acid 3-sulfate from human bile after oral administration of labeled lithocholic acid. No further information concerning sulfate esters of bile acids is available at present. 

Apparently, the requirement for a single negative charge applies primarily to the region of the side chain. The introduction of an additional negative charge at the 3-position of ring A does not preclude transport. This was demonstrated with the 3a-sulfate ester of taurolithocholic acid (24). This is one of a series of recently described natural bile salts (25). 

Nine stimuli were used. These were 3 non-familiar stimuli (amyl acetate, B-ionone, 2-phenylethanol 10 M), various relevant natural stimuli, such as 4 amino acids (L-Ala, L-Glu, L-Arg, L-Lys 10 - 10 M), a bile acid (taurolithocholic acid, I0 - 10" M), and a preovulatory pheromone (17a,20B-dihydroxy-4-pregnen-3-one, 10" - 10 M). The compounds were dissolved in tap water and for 15s repetitively applied to the olfactory epithelium. The 15s stimulus applications were interrupted by 180s tap water application of similar (1 ml/min) velocity during the interstimulus phases. 

Chemically, the bile acids are hydroxylated derivatives of cholanic acid, a tetracyclic steroid acid of 24 carbon atoms. The acids occur in nature largely as the water-soluble sodium salts of peptide conjugates of glycine and taurine. The free acids are liberated by saponification or specific enzyme hydrolysis. The chemistry of the bile acids has been reviewed in Chapter 1 of this volume (1). In view of their highly polar nature, special attention is called to the recent discovery of the cholic acid conjugates of ornithine (2, 3) and the 3a-sulfate esters of glycolithocholic and taurolithocholic acids (4). 

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. 

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