Baslow M H, Suckow R F, Sapirstein V, Hungund B L
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
J Mol Neurosci. 1999 Aug-Oct;13(1-2):47-53. doi: 10.1385/JMN:13:1-2:47.
N-acetyl-L-aspartate (NAA) is an important osmolyte in the vertebrate brain and eye, and its cyclical metabolism is accomplished in two separate compartments. In the brain, NAA is synthesized primarily in neurons, and after its regulated release, NAA is hydrolyzed by aspartoacylase, which is present in a glial-associated compartment. However, the precise nature of this hydrolytic compartment has remained obscure. It has been proposed that one role of aspartoacylase in the central nervous system (CNS) is as part of a molecular water pump (MWP) that uses the NAA intercompartmental cycle to remove nerve cell metabolic water against a water gradient and that oligodendrocytes comprise the second compartment in this metabolic sequence. The absence of aspartoacylase activity in Canavan disease (CD), a rare early onset genetic spongiform leukodystrophy, is associated with CNS edema, intramyelinic swelling and a progressive loss of oligdendrocytes. In order to evaluate the MWP hypothesis and its possible relationship to the etiology of CD further, both oligodendrocytes and astrocytes obtained from neonatal rat brain were grown in culture and tested for the presence of aspartoacylase activity. The results of this study show for the first time that aspartoacylase activity is expressed only in oligodendrocytes. The meaning of this observation in understanding the function of the NAA metabolic cycle is discussed.
N-乙酰-L-天冬氨酸（NAA）是脊椎动物大脑和眼睛中的一种重要渗透溶质，其循环代谢在两个独立的区室中完成。在大脑中，NAA主要在神经元中合成，在其受到调控释放后，NAA被天冬氨酸酰基转移酶水解，该酶存在于与神经胶质相关的区室中。然而，这个水解区室的确切性质一直不清楚。有人提出，天冬氨酸酰基转移酶在中枢神经系统（CNS）中的一个作用是作为分子水泵（MWP）的一部分，该水泵利用NAA的区室间循环逆着水梯度清除神经细胞代谢产生的水，并且少突胶质细胞构成了这个代谢序列中的第二个区室。在一种罕见的早发性遗传性海绵状脑白质营养不良——卡纳万病（CD）中，天冬氨酸酰基转移酶活性的缺失与中枢神经系统水肿、髓鞘内肿胀以及少突胶质细胞的逐渐丧失有关。为了进一步评估分子水泵假说及其与CD病因的可能关系，从新生大鼠大脑中获取的少突胶质细胞和星形胶质细胞都在培养物中生长，并检测了天冬氨酸酰基转移酶活性的存在情况。这项研究的结果首次表明，天冬氨酸酰基转移酶活性仅在少突胶质细胞中表达。讨论了这一观察结果在理解NAA代谢循环功能方面的意义。
