Aspartame Research Articles© #011 – The Effect of L-cysteine and Glutathione on Inhibition of Na+, K+-ATPase Activity by Aspartame Metabolites in Human Erythrocyte Membrane

Eur J Clin Nutr. 2006 May;60(5):593-7.

Schulpis KH, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S.

Institute of Child Health, Research Center, Aghia Sophia Children’s Hospital, Athens, Greece.

Abstract

BACKGROUND:

Reports have implicated Aspartame (N-L-a-aspartyl-L-phenylalanine methyl ester, ASP) in neurological problems.

AIM:

To evaluate Na(+), K(+)-ATPase activities in human erythrocyte membranes after incubation with the ASP metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (Asp).

METHODS:

Erythrocyte membranes were obtained from 12 healthy individuals and were incubated at 37 degrees C for 1 h with the sum or each of the ASP metabolites separately, which are commonly measured in blood after ASP ingestion. Na(+), K(+)-ATPase and Mg(2+)-ATPase activities were measured spectrophotometrically.

RESULTS:

Membrane Mg(2+)-ATPase activity was not altered. The sum of ASP metabolite concentrations corresponding to 34, 150 or 200 mg/kg of the sweetener ingestion resulted in an inhibition of the membrane Na(+), K(+)-ATPase by -30, -40, -48%, respectively. MeOH concentrations of 0.14, 0.60 or 0.80 mM decreased the enzyme activity by -25, -38, -43%, respectively. Asp concentrations of 2.80, 7.60 or 10.0 mM inhibited membrane Na(+), K(+)-ATPase by -26, -40, -46%, respectively. Phe concentrations of 0.14, 0.35 or 0.50 mM reduced the enzyme activity by -24, -44, -48%, respectively. Preincubation with L-cysteine or reduced glutathione (GSH) completely or partially restored the inhibited membrane Na(+), K(+)-ATPase activity by high or toxic ASP metabolite concentrations.

CONCLUSIONS:

Low concentrations of ASP metabolites had no effect on Na(+), K(+)-ATPase activity. High or abuse concentrations of ASP hydrolysis products significantly decreased the membrane enzyme activity, which was completely or partially prevented by L-cysteine or reduced GSH.

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