Περίληψη:
Galactosaemia is an inborn error of metabolism characterized by irreversible damage to neural tissue. To evaluate whether galactose metabolic disorders, (e.g. classical galactosaemia, galactokinase deficiency galactosaemia), is implicated for alterations of brain Mg2+-ATPase activity, various concentrations (1-16 mM) of galactose, galactose-1-phosphate, galactitol, glucose-1-phosphate or glucose were preincubated with whole brain homogenates of suckling rats at 37° for 1 hr. Mg2+-ATPase activities were determined according to Bowler & Tirri's (1974). Galactose-1-phosphate or glucose-1-phosphate excessively activated the brain Mg2+-ATPase in a concentration-dependent way. Additionally, galactitol, galactose or glucose stimulated the enzyme up to 35-45% (P<0.001) at concentrations >4 mM. A mixture of galactose-1-phosphate (2 mM), glactitol (2 mM) and galactose (4 mM), concentrations commonly found in blood and brain of untreated patients with classical galactosaemia, resulted in a 500% enzyme activation (P<0.001) as compared to control. Moreover, a mixture of galactitol (2 mM) and galactose (1 mM), concentrations measured in patients with galactokinase deficiency, caused an enzyme stimulation (35%, P<0.001). These findings suggest: a) The great Mg2+-ATPase activation by galactose-1-phosphate or glucose-1-phosphate may be due to the epimer of galactose and the presence of phosphorus. b) The brain Mg2+-ATPase stimulation by galactose and its derivatives could be toxic by modulating the Mg2+ concentration, the ATP availability, the activity of other ATP- and Mg2+-dependent enzymes as well as the rates of protein synthesis and cell growth.
Συγγραφείς:
Tsakiris, S.
Marinou, K.
Schulpis, K.H.
Λέξεις-κλειδιά:
galactitol; galactose; glucose 1 phosphate; adenosine triphosphatase (calcium magnesium); galactitol; galactose; galactose 1 phosphate; galactose phosphate; galactose-1-phosphate; glucose; glucose 1 phosphate; glucose phosphate, animal model; animal tissue; article; brain cell; brain homogenate; cell growth; concentration response; controlled study; cytotoxicity; enzyme activation; enzyme activity; female; in vitro study; male; nonhuman; priority journal; protein synthesis; rat; animal; brain; comparative study; dose response; drug effect; enzymology; metabolism; suckling; Wistar rat, Animalia, Animals; Animals, Suckling; Brain; Ca(2+) Mg(2+)-ATPase; Dose-Response Relationship, Drug; Enzyme Activation; Female; Galactitol; Galactose; Galactosephosphates; Glucose; Glucosephosphates; Male; Rats; Rats, Wistar
