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L-半胱氨酸和谷胱甘肽对阿斯巴甜代谢产物抑制人红细胞膜中钠钾ATP酶活性的影响。

The effect of L-cysteine and glutathione on inhibition of Na+, K+-ATPase activity by aspartame metabolites in human erythrocyte membrane.

作者信息

Schulpis K H, Papassotiriou I, Parthimos T, Tsakiris T, Tsakiris S

机构信息

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

出版信息

Eur J Clin Nutr. 2006 May;60(5):593-7. doi: 10.1038/sj.ejcn.1602355.

DOI:10.1038/sj.ejcn.1602355

PMID:16391576

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.

摘要

背景

有报告指出阿斯巴甜（N-L-α-天冬氨酰-L-苯丙氨酸甲酯，ASP）与神经问题有关。

目的

评估在与ASP代谢产物苯丙氨酸（Phe）、甲醇（MeOH）和天冬氨酸（Asp）孵育后，人红细胞膜中Na⁺、K⁺-ATP酶的活性。

方法

从12名健康个体获取红细胞膜，并分别与ASP代谢产物的总和或每种代谢产物在37℃孵育1小时，这些代谢产物在摄入ASP后常见于血液中。通过分光光度法测量Na⁺、K⁺-ATP酶和Mg²⁺-ATP酶的活性。

结果

膜Mg²⁺-ATP酶活性未改变。对应于摄入34、150或200mg/kg甜味剂的ASP代谢产物浓度总和分别导致膜Na⁺、K⁺-ATP酶活性抑制-30%、-40%、-48%。0.14、0.60或0.80mM的MeOH浓度分别使酶活性降低-25%、-38%、-43%。2.80、7.60或10.0mM的Asp浓度分别抑制膜Na⁺、K⁺-ATP酶-26%、-40%、-46%。0.14、0.35或0.50mM的Phe浓度分别使酶活性降低-24%、-44%、-48%。用L-半胱氨酸或还原型谷胱甘肽（GSH）预孵育可完全或部分恢复高浓度或毒性ASP代谢产物对膜Na⁺、K⁺-ATP酶活性的抑制。