Metabolic biomarkers related to energy metabolism in Saudi autistic children
Metabolic biomarkers related to energy metabolism in Saudi autistic children
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DOI：
10.1016/j.clinbiochem.2009.04.006
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发表时间：
2009-07-01
影响因子：
2.8
通讯作者：
Al-Ayadhi, L.
中科院分区：
文献类型：
--
作者：
Al-Mosalem, O. A.;El-Ansary, A.;Al-Ayadhi, L.
目的：能量代谢通常在许多神经退行性疾病中受到调控。自闭症被认为是一种可定义的系统性疾病，导致许多不同的因素，这些因素可能会影响出生前和出生后的大脑发育和功能。自闭症患病率的增加将对未来的公众产生巨大的影响，并已刺激了对潜在病因的密集研究。本研究旨在通过能量操纵的假设，建立自闭症与其伴随的退化之间的联系，特别是在大脑认知区域。材料和方法：在沙特自闭症儿童中，测量了参与人类大脑最重要的高能化合物--三磷酸腺苷产生的酶活性和途径的生化变化。测定了30例沙特自闭症患者血浆Na+/K(+)ATPase、胞外核苷酸酶(NTPDase)(ADPase和ATPase)和肌酸激酶(CK)，并与30例年龄匹配的对照组进行了比较。另外，用量热法测定两组红细胞中的腺苷单核苷酸、二核苷酸和三核苷酸(ATP、ADP和AMP)，并计算腺苷能荷(AEC)。结果：与年龄和性别匹配的健康对照组相比，自闭症患者的Na(+)K(+)ATPase和CK活性分别高出148.77%和72.35%，证明这些儿童存在能量代谢障碍。虽然ADPase在自闭症患者中显著升高，但ATPase与对照组相比没有显著升高。尽管自闭症患者的Na+/K(+)ATPase活性显著升高，但两组患者的三磷酸腺苷、腺苷二磷酸和腺苷三磷酸腺苷水平无显著差异，计算的AEC值在自闭症组和对照组分别为0.814+/-0.094和0.806+/-0.081。自闭症患者AEC值的变化与CK和ADPase的诱导活性密切相关，这两种酶对AEC的稳定起着关键作用。作为大脑重要能量代谢产物的乳酸，在自闭症患者中显着高于对照组，增加了约40%。结论：本研究证实了沙特自闭症患者的能量代谢受损，这可能与先前在同一调查样本中记录的氧化应激有关。寻找与自闭症相关的生化标志物，有利于临床早期诊断和干预。(C)2009年加拿大临床化学家协会。爱思唯尔公司出版，版权所有。
Objectives: Energy metabolism is usually manipulated in many neurodegenerative diseases. Autism is considered a definable systemic disorder resulting in a number of diverse factors that may affect the brain development and functions both pre and post natal. The increased prevalence of autism will have enormous future public implications and has stimulated intense research into potential etiologic factors. This study aims to establish a connection between autism and the deterioration accompanied it, especially in the brain cognitive areas through a postulation of energy manipulation.Materials and methods: The biochemical changes in activities of enzymes and pathways that participate in the production of ATP as the most important high-energy compound needed by the human brain were measured in Saudi autistic children. Na+/K(+)ATPase, ectonucleotidases (NTPDases) (ADPase and ATPase) and creatine kinase (CK), were assessed in plasma of 30 Saudi autistic patients and compared to 30 age-matching control samples. In addition, adenosine mono, di and trinucleotides (ATP, ADP, and AMP) were measured calorimetrically in the red blood cells of both groups and the adenylate energy charge (AEC) was calculated. Moreover, lactate concentration in plasma of both groups was monitored.Results: The obtained data recorded 148.77% and 72.35% higher activities of Na(+)K(+)ATPase and CK respectively in autistic patients which prove the impairment of energy metabolism in these children compared to age and sex matching healthy controls. While ADPase was significantly higher in autistic patients, ATPase were non-significantly elevated compared to control. In spite of the significant increase of Na+/K(+)ATPase activity in autistic patients, there was no significant difference in the levels of ATP, ADP, and AMP in both groups and the calculated AEC values were 0.814 +/- 0.094 and 0.806 +/- 0.081 for autistic and control groups respectively. The unchanged AEC value in autistic patients was easily correlated with the induced activity of CK and ADPase as two enzymes playing a critical role in the stabilization of AEC. Lactate as an important energy metabolite for the brain was significantly higher in autistic patients compared to control showing about 40% increase.Conclusion: The present study confirmed the impairment of energy metabolism in Saudi autistic patients which could be correlated to the oxidative stress previously recorded in the same investigated samples. The identification of biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. (c) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.