Al-Mosalem O A, El-Ansary A, Attas O, Al-Ayadhi L
Biochemistry Department, Science College, King Saud University, P.O Box 22452, Zip code 11495, Riyadh, Saudi Arabia.
Clin Biochem. 2009 Jul;42(10-11):949-57. doi: 10.1016/j.clinbiochem.2009.04.006. Epub 2009 Apr 17.
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.
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.
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.
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.
在许多神经退行性疾病中，能量代谢通常会受到影响。自闭症被认为是一种可明确的全身性疾病，由多种不同因素导致，这些因素可能在产前和产后影响大脑发育及功能。自闭症患病率的上升将对未来公众产生巨大影响，并激发了对潜在病因的深入研究。本研究旨在通过假设能量调控，建立自闭症与其伴随的退化之间的联系，尤其是在大脑认知区域。
在沙特自闭症儿童中测量了参与生成三磷酸腺苷（ATP，人类大脑所需的最重要高能化合物）的酶和代谢途径活性的生化变化。对30名沙特自闭症患者的血浆中的钠钾ATP酶、外核苷酸酶（NTPDases）（二磷酸腺苷酶和三磷酸腺苷酶）和肌酸激酶（CK）进行了评估，并与30份年龄匹配的对照样本进行比较。此外，用比色法测量了两组红细胞中的一磷酸腺苷、二磷酸腺苷和三磷酸腺苷（ATP、ADP和AMP），并计算了腺苷酸能量电荷（AEC）。此外，还监测了两组血浆中的乳酸浓度。
获得的数据显示，自闭症患者的钠钾ATP酶和CK活性分别比健康对照高148.77%和72.35%，这证明与年龄和性别匹配的健康对照相比，这些儿童存在能量代谢受损。虽然自闭症患者的二磷酸腺苷酶显著升高，但三磷酸腺苷酶与对照组相比升高不显著。尽管自闭症患者的钠钾ATP酶活性显著增加，但两组的ATP、ADP和AMP水平没有显著差异，自闭症组和对照组计算出的AEC值分别为0.814±0.094和0.806±0.081。自闭症患者中不变的AEC值很容易与肌酸激酶和二磷酸腺苷酶的诱导活性相关，这两种酶在AEC的稳定中起关键作用。作为大脑重要能量代谢物的乳酸，在自闭症患者中显著高于对照组，增加了约40%。
本研究证实沙特自闭症患者存在能量代谢受损，这可能与之前在相同研究样本中记录的氧化应激有关。识别与自闭症相关的生化标志物将有利于早期临床诊断和干预。
