Friedreich's ataxia II. Biochemical studies in cultured cells

Abstract

Pyruvate and palmitate oxidations by cultured fibroblast suspensions were measured in optimized conditions and proved to be with normal range in the cells from Friedreich's patients. But when pyruvate oxidation was measured by direct assay of the pyruvate dehydrogenase complex, this enzyme activity proved to be significantly lower in Friedreich's than in controls' cells. These abnormalities were not observed when the cells were sonicated. Moreover, lipoamide dehydrogenase activity Km and Vmax were within the normal range in Friedreich's cells. These data suggest that the low activities of the PDH complex are not a primary defect in Friedreich's ataxia but are more likely to be related to membrane abnormalities in Friedreich's cells.

Sommario

L'ossidazione del piruvato e del palmitato misurata nei fibroblasti in cultura di pazienti affetti da malattia di Friedreich è risultata normale.

Il dosaggio del complesso enzimatico piruvico deidrogenasi è invece risultato significativamente diminuito rispetto ai controlli nelle cellule di questi pazienti quando i fibroblasti venivano omogenizzati in glicerolo. Questa diminuzione però non era più evidente se le cellule venivano sonicate.

Questi dati suggeriscono che il deficit del complesso PDH nei pazienti con atassia di Freidreich non sia un difetto primario ma rifletta piuttosto anomalie di membrana.