Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: Implications for specialized acetyl coenzyme A metabolism in the CNS
Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: Implications for specialized acetyl coenzyme A metabolism in the CNS
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DOI：
10.1016/j.brainres.2010.04.008
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发表时间：
2010-06-04
期刊：
影响因子：
2.9
通讯作者：
Namboodiri, Aryan M. A.
中科院分区：
文献类型：
--
作者：
Ariyannur, Prasanth S.;Moffett, John R.;Namboodiri, Aryan M. A.
N-乙酰天冬氨酸（NAA）是一种浓缩的神经元特异性脑代谢物，通常用作脑损伤和疾病的磁共振波谱标记物。尽管几十年的研究，NAA的功能作用仍然不清楚。几十年来的生物化学研究已经将NAA与髓鞘脂质合成和能量代谢联系起来。然而，由于无法鉴定NAA生物合成酶天冬氨酸N-乙酰转移酶（Asp-NAT）的基因，研究受到阻碍。最近的一份报告已经确定Nat 8l为编码Asp-NAT的基因，并证实在脑磁共振波谱图上被诊断为缺乏NAA的唯一儿童在该基因中有19 bp的缺失。基于体外Nat 8l表达研究，研究人员得出结论，许多以前的生化研究在技术上存在缺陷，NAA可能与大脑能量或脂质代谢无关。在我们实验室同时进行的研究中，我们已经证明，通过克隆，表达，特异性乙酰化的天冬氨酸，甲基苯丙胺治疗的反应，分子建模和比较免疫定位，NAT 8L是NAA生物合成酶Asp-NAT。我们的结论是，NAA是一个主要的存储和运输形式的乙酰辅酶A特定的神经系统，从而将其连接到脂质合成和能量代谢。出版社：Elsevier BM
N-acetylaspartate (NAA) is a concentrated, neuron-specific brain metabolite routinely used as a magnetic resonance spectroscopy marker for brain injury and disease. Despite decades of research, the functional roles of NAA remain unclear. Biochemical investigations over several decades have associated NAA with myelin lipid synthesis and energy metabolism. However, studies have been hampered by an inability to identify the gene for the NAA biosynthetic enzyme aspartate N-acetyltransferase (Asp-NAT). A very recent report has identified Nat8l as the gene encoding Asp-NAT and confirmed that the only child diagnosed with a lack of NAA on brain magnetic resonance spectrograms has a 19-bp deletion in this gene. Based on in vitro Nat8l expression studies the researchers concluded that many previous biochemical investigations have been technically flawed and that NAA may not be associated with brain energy or lipid metabolism. In studies done concurrently in our laboratory we have demonstrated via cloning, expression, specificity for acetylation of aspartate, responsiveness to methamphetamine treatment, molecular modeling and comparative immunolocalization that NAT8L is the NAA biosynthetic enzyme Asp-NAT. We conclude that NAA is a major storage and transport form of acetyl coenzyme A specific to the nervous system, thus linking it to both lipid synthesis and energy metabolism. Published by Elsevier BM.