Possible explanations for the differences in secretory characteristics between conjugated and free bile acids.

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Abstract
The hepatic extraction fraction and maximum excretory rate of conjugated cholate were greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of unionized cholic acid (pKa 5.5) compared to that of taurocholic acid (pKa 2) was investigated by varying the pH of bile by secretin or acetazolamide administration in the anesthetized dog. The mean biliary pH during free cholate excretion in the control state in 23 experiments was 7.5 (at which approximately 1% of cholate is unionized). Three to 4-fold changes in the H+ activity of bile (which resulted in changes of the same magnitude in the percentage of unionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. Back-diffusion of unionized cholic acid in the bile ducts was not an important determinant of the secretory performance of free cholate. The bile flow rate associated with mainly free cholate excretion was much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appeared to arise largely by means that were independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free cholate was only slightly greater than that of bile containing mainly taurocholate at the same total cholate concentration. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about 1/5 of the maximum rate attainable; at the peak rate taurocholate was almost completely removed in the 1st passage of blood through the liver.