ROLE OF CYSTEINE AND TAURINE IN REGULATING GLUTATHIONE SYNTHESIS BY PERIPORTAL AND PERIVENOUS HEPATOCYTES

The uptake and metabolism of 35S-labelled sulphur amino acids were compared in periportal (PP) and perivenous (PV) rat hepatocytes, isolated by digitonin/collagenase perfusion, to identify the factors underlying the previously observed [Kera, Penttila and Lindros, Biochem. J. (1988) 254, 411-417] higher rate of GSH replenishment in PP cells. The buthionine sulphoximine-inhibitable synthesis of GSH was faster in PP than in PV hepatocytes with both cysteine (6.1 versus 5.0 μmol/h per g of cells) and methionine (4.5 versus 3.3 μmol/h per g) as well as with endogenous precursor and L-2-oxo-4-thiazolidinecarboxylate as substrates. However, the uptake of cysteine by PP cells was slower than by PV cells (8.6 versus 10.3 μmol/h per g of cells), whereas methionine was taken up at similar rates. The activity of γ-glutamylcysteine synthetase (GCS) was slightly higher in digitonin lysates from the PP than from the PV zone. Production of sulphate, the major catabolite of [35S]cysteine sulphur, as well as incorporation of the label into protein occurred at similar rates in PP and PV cells. Taurine, on the other hand, was produced from [35S]cysteine much faster by PV than by PP cells (0.7 versus 0.1 μmol/h per g of cells). Acccordingly, the taurine content of PV hepatocytes tended to be higher and to increase faster during incubation with methionine. These results imply that metabolism of taurine is higly zonated within the acinus. They also suggest that both the slightly lower GSC activity and the fast metabolism of cysteine to taurine limit the capacity of PV hepatocytes to synthesize GSH.