The hepatic extraction of unconjugated and taurineconjugated bile acids, provided with different hydrophilicity values, has been measured in the perfused rat liver, in order to evaluate the role of the bile acid structure and bile acid hydrophilicity on their uptake by the liver. Ursocholic, cholic, ursodeoxycholic and chenodeoxycholic acids, free and taurine-conjugated, were injected into the portal vein in dose response studies, using a nonrecirculating perfusion system.
For all of the bile acids, the uptake process showed saturation.
In addition, a nonsaturable component was apparent in bile acids provided with the lowest hydrophilicity values, as expressed by the lowest values of the water to octanol partition coefficient. The maximum uptake velocity increased with increasing values of the partition coefficient, which in turn were associated with 7-OH α to β epimerization, the presence of 12-OH in α position and taurine conjugation. The ratio of maximum uptake velocity to Km (Km being the half-saturation constant) appeared to be markedly increased by taurine conjugation and by 7-OH α to β epimerization, whereas it was reduced by the presence of 12-OH in α position.
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