Insights into Taurine Synthesis and Function Based on Studies with Cysteine Dioxygenase (CDO1) Knockout Mice

Abstract

Cysteine is metabolized to cysteinesulfinate by cysteine dioxygenase (CDO), which is encoded by the Cdo1 gene. This CDO-mediated pathway is the dominant pathway for biosynthesis of taurine in mammals. Studies with Cdo1 ^−/− mice offer new insights about taurine synthesis and function. Taurine and hypotaurine levels in 8-week old Cdo1 ^−/− mice, which had access to taurine only from their heterozygous (Cdo1 ^+/−) dams during gestation and suckling, were very low compared to levels in wild-type mice fed the same taurine-free diet. On the other hand, hepatocyte-specific disruption of Cdo1 did not result in taurine or hypotaurine depletion in liver; and plasma, kidney and pancreas hypotaurine levels were actually significantly increased along with increased abundance of CDO in these extrahepatic tissues, demonstrating the capacity of extrahepatic tissues to compensate for the loss of hepatic CDO. Unexpectedly, hypotaurine levels varied markedly among tissues in wild-type mice and were particularly high in the pancreas; hypotaurine levels in the pancreas were 65-times those in liver, and hypotaurine as a percentage of taurine content of the same tissue (on a molar basis) was 60 % in pancreas but less than 1 % in liver. Lack of CDO and low tissue taurine levels were also associated with increases in unconjugated and glycine-conjugated bile acid concentrations and increases in concentrations of other potential organic osmolytes.