Cystine, cysteine and glutathione metabolism in normal and cystinotic fibroblasts in vitro and in cultured normal amniotic fluid cells

Abstract

The intracellular concentrations of reduced cysteine and glutathione are normal in cystinotic fibroblasts, even though they contain a marked increase in cystine. Cystine accumulation is thus not attributable to an elevated concentration of cysteine with secondary cystine formation, nor can it result from a decreased concentration of reduced glutathione, which acts as a hydrogen donor in transhydrogenation reactions for maintaining intracellular cyst(e)ine in its reduced state. The rates of turnover of glutathione in cystinotic and normal fibroblasts are similar, with half-lives of about 6–8 h. The intracellular cystine pool in cystinotic cells has a half-life of approximately 6 h, indicating that while compartmentalized, it remains in a state of dynamic equilibrium with exogenous cystine. The intracellular cysteine and glutathione levels in normal amniotic fluid cells are similar to those in fibroblasts. This suggests that the metabolism of these substances is similar in both types of cells, and strengthens earlier suggestions that cultured amniotic fluid cells may be used for the prenatal diagnosis of cystinosis, as fibroblasts are now used for its diagnosis postnatally.