Inhibition of creatine kinase activity by lysine in rat cerebral cortex

Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS Brazil; Universidade luterana do Brasil, Canoas, RS Brazil
Metabolic Brain Disease (Impact Factor: 2.33). 24(2):349-360. DOI: 10.1007/s11011-009-9131-z

ABSTRACT 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 14CO2 production from [U-14C] glucose (aerobic glycolytic pathway) and [1-14C] 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 5.0mM. 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.

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