Accumulation of
lysine (Lys) in tissues and biochemical fluids is the biochemical hallmark of patients affected by
familial hyperlysinemia (FH) and also by other inherited neurometabolic disorders. In the present study, we investigated the in vitro effect of Lys on various parameters of energy metabolism in cerebral cortex of 30-day-old Wistar rats. We verified that total (tCK) and cytosolic
creatine kinase activities were significantly inhibited by Lys, in contrast to the mitochondrial
isoform which was not affected by this
amino acid. Furthermore, the inhibitory effect of Lys on tCK activity was totally prevented by
reduced glutathione, suggesting a possible role of reactive species oxidizing critical
thiol groups of the
enzyme. In contrast, Lys did not affect (14)CO(2) production from [U-(14)C]
glucose (aerobic glycolytic pathway) and [1-(14)C]
acetic acid (citric acid cycle activity) neither the various activities of the electron transfer chain and synaptic Na(+)K(+)-
ATPase at concentrations as high as 5.0 mM. Considering the importance of
creatine kinase (CK) activity for brain energy metabolism homeostasis and especially
ATP transfer and buffering, our results suggest that inhibition of this
enzyme by Lys may contribute to the neurological signs presented by symptomatic patients affected by FH and other
neurodegenerative disorders in which Lys accumulates.