Zonal distribution of cysteine uptake in the perfused rat liver

When in situ perfused rat livers were administered tracer or physiologic concentrations of [35S]cysteine, a zone III (perivenous) predominance of uptake was observed in either antegrade or retrograde single-pass perfusion, as determined by quantitative densitometry of autoradiographs of liver section. This pattern remained unchanged from 30 s to 5 min observed. At higher supraphysiologic doses a more uniform acinar distribution of cysteine uptake was observed. Uptake rates of cysteine in antegrade perfusion indicated an apparent saturable component at low but physiologic cysteine concentrations. That uptake rather than metabolic trapping accounts for this perivenular pattern was supported by finding identical zonal distribution under conditions in which GSH and protein synthesis were markedly inhibited. Furthermore, increasing or decreasing hepatic cysteine pool sizes did not affect the extraction or zonation. These results suggest that a low Km transport system for cysteine is localized in zone III of the hepatic acinus.