l-Aspartate (aspartic acid; C4H7NO4;
2-aminobutanedoic acid) is a non-essential α-amino acid found
ubiquitously throughout the body, including in the brain. Aspartate is
one of the protein-forming amino acids and the formation of
tRNA-aspartate complex is catalysed by aspartyl tRNA synthetase. Free
aspartate, which is the main subject of this review, plays key roles in
metabolism, as an amino donor and acceptor. It contributes to the
synthesis of protein, arginine and nitric oxide, asparagine, N-acetylaspartate and N-methyl-d-aspartate.
Its major metabolic role in the brain is recycling reducing equivalents
(protons) between the cytoplasm and mitochondrial matrix as part of the
malate-aspartate shuttle. l-Aspartate’s
actions on synaptic receptors, as well as its possible presence in
nerve terminals and synaptic vesicles, are, in principle, consistent
with a role as an excitatory neurotransmitter. The evidence is far from
conclusive and at times controversial. The role of d-aspartate in brain function is even less certain but, it appears that, rather than being a minor neurotransmitter, d-aspartate
is more likely to be involved in fine regulation of endocrine and
homeostatic processes. Much research remains to be done in this area.
The diversity of its functions and chemistry make aspartate a complex
molecule to investigate and measure in vivo. Perturbations of aspartate
metabolism have been described in a range of neurological deficits,
particularly those of white matter. Here, we examine what is known about
the various roles of aspartate in brain, its metabolism, transport and
compartmentation, its role as a neurotransmitter or a more general
signalling molecule, and what is currently known about its role(s) in
disease processes.
More at link.
Malate Aspartate Shuttle—Linkage to Phosphorylation State
The malate-aspartate shuttle (Fig. 1) plays a major role in the movement of reducing equivalents (NADH) into, or out of, the mitochondrion.
