NAA synthesis and functional roles.
NAA synthesis and functional roles.
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NAA 合成和功能作用。
DOI：
10.1007/0-387-30172-0_4
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发表时间：
2006
影响因子：
--
通讯作者：
Namboodiri,AryanMA
中科院分区：
文献类型：
--
作者：
Madhavarao,ChikkathurN;Namboodiri,AryanMA
大约 50 年前，Tallan1 报道了猫脑中存在高浓度 (10-14 mM) N-乙酰天冬氨酸 (NAA)。经过很长一段时间的差距后，过去 20 年取得了巨大进展，发现了卡纳万病 2、3 中的 NAA 代谢缺陷，以及使用磁共振波谱法认识到 NAA 作为神经元健康指标的价值。 4-7 然而，NAA 合成的生化机制仍不清楚。关于 NAA 合成酶及其在线粒体亚细胞定位的早期报告于 1979 年提出。 11 合成酶 L-天冬氨酸 N-乙酰转移酶（Asp-NAT；EC 2.3. 1.17）直到最近才被鉴定为可能来自大鼠大脑的多亚基酶复合物。 12 然而，该酶的进一步分子表征仍有待完成。虽然许多报告表明 NAA 主要定位于中枢神经系统 (CNS) 的神经元中，5, 13-15 NAA 水解酶天冬氨酸酰化酶（酰胺水解酶 2，ASPA；EC 3.5. 1.15）主要定位于少突胶质细胞，即 CNS 中的髓鞘形成细胞。 16-19 与 Asp-NAT 不同，NAA 水解酶 ASPA 首次在猪肾中被报道后，已有大量文献报道。 20 随后在脑组织中检测到 ASPA21，并随后从牛脑中纯化。 22 这项工作导致了编码 ASPA23 的基因序列的鉴定以及人类和小鼠重组基因的克隆和表达。 24, 25 编码 ASPA 的基因突变与致命的遗传性疾病卡纳万病有关。 3、26、27
Tallan1 reported the occurrence of high concentrations (10-14 mM) of N-acetylaspartate (NAA) in cat brain almost 50 years ago. After a long gap, the past 20 years have seen tremendous progress with discoveries such as the NAA metabolic defect in Canavan disease2, 3 and the recognition of the value of NAA as an index of neuronal health using magnetic resonance spectroscopy. 4-7 However, the biochemical mechanisms of NAA synthesis remain unclear. The early reports on the NAA synthetic enzyme date 8-10 and its subcellular localization to mitochondria was indicated in 1979. 11 The synthetic enzyme, L-Aspartate N-acetyltransferase (Asp-NAT; EC 2.3. 1.17) was characterized only recently as a possible multi-subunit enzyme complex from rat brain. 12 However, further molecular characterization of this enzyme remains to be accomplished.While a number of reports indicate that NAA is localized primarily in neurons in the central nervous system (CNS), 5, 13-15 the NAA hydrolyzing enzyme aspartoacylase (amidohydrolase 2, ASPA; EC 3.5. 1.15) has been localized primarily in oligodendrocytes, the myelinating cells in the CNS. 16-19 Unlike Asp-NAT, there has been a body of literature available on the NAA hydrolyzing enzyme, ASPA, after it was first reported in hog kidney. 20 ASPA was later detected in brain tissue21 and it was subsequently purified from bovine brain. 22 This work led to the identification of the genetic sequence coding ASPA23 and cloning and expression of human and mouse recombinant genes. 24, 25 Mutations in the gene coding ASPA have been linked to the fatal genetic disorder, Canavan disease. 3, 26, 27