Schulpis Kleopatra H, Michelakakis Helen, Tsakiris Theodore, Tsakiris Stylianos
Institute of Child Health, "Aghia Sophia" Children's Hospital, GR-11527 Athens, Greece.
Clin Nutr. 2005 Feb;24(1):151-7. doi: 10.1016/j.clnu.2004.09.001.
Classical galactosaemia is characterized by high levels of galactose-1-phosphate (Gal-1-P), galactose and galactitol. In vitro studies have shown modulation of the rat brain Na+,K+-ATPase and Mg2+-ATPase activities by Gal-1-P. The aim of this study was to evaluate the erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in galactosaemic patients and to correlate them to Gal-1-P, total antioxidant status (TAS) and membrane protein content (PC).
Nine patients (N=9) originally on "loose diet" (group B) were requested to follow their diet strictly (group A). Twelve healthy children were the controls (group C). The activities of the enzymes, TAS and Gal-1-P in blood were determined spectrophotometrically. In the in vitro study, erythrocyte membranes from controls were preincubated with Gal-1-P (300 microM), and then with l-cysteine (0.83 mM) or reduced glutathione (0.83 mM) whereas these from the patients with the antioxidants only.
Na+,K+-ATPase, Mg2+-ATPase, TAS and PC were significantly (P<0.001) reduced (0.31+/-0.03, 1.7+/-0.2 micromol Pi/hxmg protein, 0.89+/-0.02 mmol/l, 36.8+/-2.0 g/l, respectively) in group B as compared with those of group A (0.58+/-0.06, 2.5+/-0.2 micromol Pi/hxmg protein, 1.41+/-0.11 mmol/l, 51.5+/-3.1g/l, respectively) and controls (0.67+/-0.05, 3.2+/-0.2 micromol Pi/hxmg protein, 1.65+/-0.12 mmol/l, 64.0+/-3.5 g/l, respectively). Gal-1-P levels in group B was significantly higher than those in group A and controls. Positive correlation coefficients were found between the enzyme activities, PC and TAS whereas Gal-1-P inversely correlated to the enzyme activities. Incubation of the erythrocyte membranes from the patients with the antioxidants failed to restore the activities of inhibited enzymes, whereas the inhibition by Gal-1-P in controls was reversed.
High blood Gal-1-P concentrations resulted in low TAS and PC. The inhibition of Na+,K+-ATPase and Mg2+-ATPase may be due to the presence of free radicals and/or the elevated Gal-1-P.
经典型半乳糖血症的特征是半乳糖-1-磷酸（Gal-1-P）、半乳糖和半乳糖醇水平升高。体外研究表明Gal-1-P可调节大鼠脑钠钾ATP酶和镁ATP酶的活性。本研究旨在评估半乳糖血症患者红细胞膜钠钾ATP酶和镁ATP酶的活性，并将其与Gal-1-P、总抗氧化状态（TAS）和膜蛋白含量（PC）相关联。
9名最初采用“宽松饮食”的患者（B组）被要求严格遵循饮食（A组）。12名健康儿童作为对照组（C组）。采用分光光度法测定血液中酶、TAS和Gal-1-P的活性。在体外研究中，对照组的红细胞膜先用Gal-1-P（300μM）预孵育，然后用L-半胱氨酸（0.83 mM）或还原型谷胱甘肽（0.83 mM）孵育，而患者的红细胞膜仅用抗氧化剂孵育。
与A组（分别为0.58±0.06、2.5±0.2微摩尔Pi/小时×毫克蛋白、1.41±0.11毫摩尔/升、51.5±3.1克/升）和对照组（分别为0.67±0.05、3.2±0.2微摩尔Pi/小时×毫克蛋白、1.65±0.12毫摩尔/升、64.0±3.5克/升）相比，B组的钠钾ATP酶、镁ATP酶、TAS和PC显著降低（分别为0.31±0.03、1.7±0.2微摩尔Pi/小时×毫克蛋白、0.89±0.02毫摩尔/升、36.8±2.0克/升）。B组的Gal-1-P水平显著高于A组和对照组。酶活性、PC和TAS之间存在正相关系数，而Gal-1-P与酶活性呈负相关。用抗氧化剂孵育患者的红细胞膜未能恢复被抑制酶的活性，而Gal-1-P对对照组的抑制作用被逆转。
高血Gal-1-P浓度导致低TAS和PC。钠钾ATP酶和镁ATP酶的抑制可能是由于自由基的存在和/或Gal-1-P升高。
Zotero 插件