Cystinosis is a disorder associated with excessive lysosomal
cystine accumulation secondary to defective
cystine efflux. Patients affected by this disease develop a variable degree of symptoms depending on the involved tissues. Accumulation of
cystine in myocardium may lead to
heart failure. However, the mechanisms by which
cystine is toxic to the tissues are not fully understood. Considering that thiolic
enzymes like
pyruvate kinase (PK) may be altered by
disulfides like
cystine, the main objective of the present study was to investigate the effect of
cystine on PK activity in the heart of developing rats. We performed kinetic studies and investigated the effects of
reduced glutathione (GSH), a biologically occurring
thiol groups protector, and
cysteamine, the
drug used for
cystinosis treatment, on the
enzyme activity. We observed that
cystine inhibited the
enzyme activity non-competitively in a dose- and time-dependent way. We also observed that GSH and
cysteamine fully prevented and reversed the inhibition caused by
cystine, suggesting that
cystine inhibits PK activity by oxidation of the sulfhydryl groups of the
enzyme. Although there is no definite proof of
cystine within cytoplasm, there is indirect proof t it is able to escape lysosomes and come in contact with PK. Considering that
cysteamine is used in patients with
cystinosis because it causes parenchymal organ
cystine depletion, the present data provide a possible new effect for this
drug.