Evidence supporting a role for N-acetyl-L-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review

Abstract

Molecular water pumps (MWPs) are characterized as biochemical systems existing at a compartmental boundary of living cells that can actively pump water against its gradient. A role for the observed intercompartmental transport of N-acetyl-L-aspartate (NAA), between neurons and oligodendrocytes in the CNS, as an efflux MWP for the removal of neuronal metabolic water has been proposed. In this review, accumulating evidence in support of such a role for NAA is presented, and the dynamics of the NAA cycle in myelinated neurons are considered. Based on the results of recent investigations, it is calculated that 1 mol of NAA is synthesized for every 40 mol of glucose (Glc) equivalent oxidized in the brain, and each mol of NAA may transport 121 mol of metabolic water out of neurons. In addition, turnover of total brain NAA is very rapid and appears to be only 16.7 h. Thus, the most important characteristic of NAA in the brain may not be its static level, but a dynamic aspect related to its rapid turnover. The relationship of NAA as a potential MWP to Canavan disease (CD), a genetic spongiform leukodystrophy in which the catabolic portion of the NAA cycle is deficient, and in a newly recognized brain disorder, hypoacetylaspartia, where the anabolic portion of the NAA cycle appears to be deficient, are discussed.