[⁷⁵Se]-Selenohomotaurocholic Acid Degradation by Bacterial Enzymes in vitro and in vivo

Abstract

The stability of the bile acid analogue [⁷⁵Se]-selenohomotaurocholic acid (⁷⁵SeH-CAT) was studied in man. When ⁷⁵SeHCAT was administered to patients for diagnostic purposes the majority of labeled material present in the feces was found deconjugated. In vitro incubation of ⁷⁵SeHCAT, by addition of fecal homogenate or with addition of purified enzyme, showed identical deconjugation. The relative differences in polarities of ⁷⁵SeHCAT, [⁷⁵Se]-selenohomocholic acid (⁷⁵SeHCA), [¹⁴C]-taurocholic acid (¹⁴C-TCA) and [¹⁴C]-cholic acid (¹⁴C-CA) were estimated by isoelectric focusing and selective chloroform extractions at various pH values. The pi values representing the pH where these molecules become uncharged were for ⁷⁵SeHCA and ⁷⁵SeHCAT 3.1, for ¹⁴C-TCA 3.0 and for ¹⁴C-CA 3.9. These results suggest that from these bile acids only ¹⁴C-CA is a candidate for passive absorption in the colon, while ⁷⁵SeHCA would be far too polar for passive diffusion. Indeed, we could demonstrate the inability of ⁷⁵SeHCA for passive absorption in healthy persons. In conclusion, ⁷⁵SeHCAT, specifically selected to monitor active ileal bile acid transport, functions as a good indicator of this process in its conjugated form. In contrast to published data it is susceptible to bacterial degradation, and therefore gives rise to a diminished whole-body retention.