N-Acetylaspartic acid

Last updated
N-Acetylaspartic acid
Acetylaspartate.png
Names
IUPAC name
2-Acetamidobutanedioic acid [1]
Identifiers
3D model (JSmol)
3DMet
1726198 S
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.012.403 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 219-827-5
KEGG
MeSH N-acetylaspartate
PubChem CID
RTECS number
  • CI9098600
UNII
  • InChI=1S/C6H9NO5/c1-3(8)7-4(6(11)12)2-5(9)10/h4H,2H2,1H3,(H,7,8)(H,9,10)(H,11,12) X mark.svgN
    Key: OTCCIMWXFLJLIA-UHFFFAOYSA-N X mark.svgN
  • CC(=O)N[C@@H](CC(=O)O)C(=O)O
Properties
C6H9NO5
Molar mass 175.140 g·mol−1
AppearanceColourless, transparent crystals
Melting point 137 to 140 °C (279 to 284 °F; 410 to 413 K)
Boiling point 141 to 144 °C (286 to 291 °F; 414 to 417 K)
log P −2.209
Acidity (pKa)3.142
Basicity (pKb)10.855
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
Related compounds
Related alkanoic acids
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

N-Acetylaspartic acid, or N-acetylaspartate (NAA), is a derivative of aspartic acid with a formula of C6H9NO5 and a molecular weight of 175.139.

Contents

NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons, [2] oligodendrocytes and myelin [3] and is synthesized in the mitochondria from the amino acid aspartic acid and acetyl-coenzyme A. [4]

Function

The various functions served by NAA are under investigation, but the primary proposed functions include:

In the brain, NAA was thought to be present predominantly in neuronal cell bodies, where it acts as a neuronal marker, [5] but it is also free to diffuse throughout neuronal fibers. [6]

Applications

However, the recent discovery of a higher concentration of NAA in myelin and oligodendrocytes than in neurons raises questions about the validity of the use of NAA as a neuronal marker. [3] NAA gives off the largest signal in magnetic resonance spectroscopy of the human brain. The levels measured there are decreased in numerous neuropathological conditions ranging from brain injury to stroke to Alzheimer's disease. This fact makes NAA a potential diagnostic molecule for doctors treating patients with brain damage or disease.

NAA may be a marker of creativity. [7] High NAA levels in the hippocampus are related to better working memory performance in humans. [8] Whole-brain levels of NAA have also been found to be positively correlated with educational attainment in adults. [9]

NAA may function as a neurotransmitter in the brain by acting on metabotropic glutamate receptors. [10]

See also

Related Research Articles

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

Within a nervous system, a neuron, neurone, or nerve cell is an electrically excitable cell that fires electric signals called action potentials across a neural network. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

Canavan disease, or Canavan–Van Bogaert–Bertrand disease, is a rare and fatal autosomal recessive degenerative disease that causes progressive damage to nerve cells and loss of white matter in the brain. It is one of the most common degenerative cerebral diseases of infancy. It is caused by a deficiency of the enzyme aminoacylase 2, and is one of a group of genetic diseases referred to as leukodystrophies. It is characterized by degeneration of myelin in the phospholipid layer insulating the axon of a neuron and is associated with a gene located on human chromosome 17.

<span class="mw-page-title-main">Glutamic acid</span> Amino acid and neurotransmitter

Glutamic acid is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABAergic neurons.

<i>N</i>-Methyl-<small>D</small>-aspartic acid Amino acid derivative

N-methyl-D-aspartic acid or N-methyl-D-aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike glutamate, NMDA only binds to and regulates the NMDA receptor and has no effect on other glutamate receptors. NMDA receptors are particularly important when they become overactive during, for example, withdrawal from alcohol as this causes symptoms such as agitation and, sometimes, epileptiform seizures.

<span class="mw-page-title-main">Oligodendrocyte</span> Neural cell type

Oligodendrocytes, also known as oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons within the central nervous system (CNS) of jawed vertebrates. Their function is similar to that of Schwann cells, which perform the same task in the peripheral nervous system (PNS). Oligodendrocytes accomplish this by forming the myelin sheath around axons. Unlike Schwann cells, a single oligodendrocyte can extend its processes to cover around 50 axons, with each axon being wrapped in approximately 1 μm of myelin sheath. Furthermore, an oligodendrocyte can provide myelin segments for multiple adjacent axons.

<span class="mw-page-title-main">Astrocyte</span> Type of brain cell

Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to around 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.

<span class="mw-page-title-main">Excitotoxicity</span> Process that kills nerve cells

In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA in subtoxic amounts induces neuronal survival of otherwise toxic levels of glutamate.

<span class="mw-page-title-main">Kainic acid</span> Chemical compound

Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervous system. Glutamate is produced by the cell's metabolic processes and there are four major classifications of glutamate receptors: NMDA receptors, AMPA receptors, kainate receptors, and the metabotropic glutamate receptors. Kainic acid is an agonist for kainate receptors, a type of ionotropic glutamate receptor. Kainate receptors likely control a sodium channel that produces excitatory postsynaptic potentials (EPSPs) when glutamate binds.

<span class="mw-page-title-main">Metabotropic glutamate receptor</span> Type of glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.

<span class="mw-page-title-main">Glutamate receptor</span> Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells

Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.

<span class="mw-page-title-main">Aspartoacylase</span> Hydrolytic enzyme encoded on human chromosome 17

Aspartoacylase is a hydrolytic enzyme that in humans is encoded by the ASPA gene. ASPA catalyzes the deacylation of N-acetyl-l-aspartate (N-acetylaspartate) into aspartate and acetate. It is a zinc-dependent hydrolase that promotes the deprotonation of water to use as a nucleophile in a mechanism analogous to many other zinc-dependent hydrolases. It is most commonly found in the brain, where it controls the levels of N-acetyl-l-aspartate. Mutations that result in loss of aspartoacylase activity are associated with Canavan disease, a rare autosomal recessive neurodegenerative disease.

<span class="mw-page-title-main">Quisqualic acid</span> Chemical compound

Quisqualic acid is an agonist of the AMPA, kainate, and group I metabotropic glutamate receptors. It is one of the most potent AMPA receptor agonists known. It causes excitotoxicity and is used in neuroscience to selectively destroy neurons in the brain or spinal cord. Quisqualic acid occurs naturally in the seeds of Quisqualis species.

<span class="mw-page-title-main">Excitatory amino acid transporter 1</span> Protein found in humans

Excitatory amino acid transporter 1 (EAAT1) is a protein that, in humans, is encoded by the SLC1A3 gene. EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1).

<i>N</i>-Acetylaspartylglutamic acid Peptide neurotransmitter

N-Acetylaspartylglutamic acid is a peptide neurotransmitter and the third-most-prevalent neurotransmitter in the mammalian nervous system. NAAG consists of N-acetylaspartic acid (NAA) and glutamic acid coupled via a peptide bond.

<span class="mw-page-title-main">Excitatory amino acid transporter 3</span> Protein found in humans

Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene.

In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system. Neurons are unable to synthesize either the excitatory neurotransmitter glutamate, or the inhibitory GABA from glucose. Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes. The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA.

An excitatory amino acid reuptake inhibitor (EAARI) is a type of drug which inhibits the reuptake of the excitatory neurotransmitters glutamate and aspartate by blocking one or more of the excitatory amino acid transporters (EAATs).

<span class="mw-page-title-main">Glutamate (neurotransmitter)</span> Anion of glutamic acid in its role as a neurotransmitter

In neuroscience, glutamate is the anion of glutamic acid in its role as a neurotransmitter. It is by a wide margin the most abundant excitatory neurotransmitter in the vertebrate nervous system. It is used by every major excitatory function in the vertebrate brain, accounting in total for well over 90% of the synaptic connections in the human brain. It also serves as the primary neurotransmitter for some localized brain regions, such as cerebellum granule cells.

<span class="mw-page-title-main">Spongy degeneration of the central nervous system</span> Neurodegenerative disorder

Spongy degeneration of the central nervous system, also known as Canavan's disease, Van Bogaert-Bertrand type or Aspartoacylase (AspA) deficiency, is a rare autosomal recessive neurodegenerative disorder. It belongs to a group of genetic disorders known as leukodystrophies, where the growth and maintenance of myelin sheath in the central nervous system (CNS) are impaired. There are three types of spongy degeneration: infantile, congenital and juvenile, with juvenile being the most severe type. Common symptoms in infants include lack of motor skills, weak muscle tone, and macrocephaly. It may also be accompanied by difficulties in feeding and swallowing, seizures and sleep disturbances. Affected children typically die before the age of 10, but life expectancy can vary.

References

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  2. Simmons ML, Frondoza CG, Coyle JT (1991). "Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies". Neuroscience. 45 (1): 37–45. doi:10.1016/0306-4522(91)90101-s. PMID   1754068. S2CID   24071454.
  3. 1 2 Nordengen K, Heuser C, Rinholm JE, Matalon R, Gundersen V (March 2015). "Localisation of N-acetylaspartate in oligodendrocytes/myelin". Brain Structure & Function. 220 (2): 899–917. doi:10.1007/s00429-013-0691-7. PMID   24379086. S2CID   475973.
  4. Patel TB, Clark JB (December 1979). "Synthesis of N-acetyl-L-aspartate by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport". The Biochemical Journal. 184 (3): 539–46. doi:10.1042/bj1840539. PMC   1161835 . PMID   540047.
  5. Chatham JC, Blackband SJ (2001). "Nuclear magnetic resonance spectroscopy and imaging in animal research". ILAR Journal. 42 (3): 189–208. doi: 10.1093/ilar.42.3.189 . PMID   11406719.
  6. Najac C, Branzoli F, Ronen I, Valette J (April 2016). "Brain intracellular metabolites are freely diffusing along cell fibers in grey and white matter, as measured by diffusion-weighted MR spectroscopy in the human brain at 7 T". Brain Structure & Function. 221 (3): 1245–54. doi:10.1007/s00429-014-0968-5. PMC   4878649 . PMID   25520054.
  7. Geddes, Linda. "Creativity chemical favours the smart".
  8. Kozlovskiy S, Vartanov A, Pyasik M, Polikanova I (2012). "Working memory and N-acetylaspartate level in hippocampus, parietal cortex and subventricular zone". International Journal of Psychology. 47: 584. doi: 10.1080/00207594.2012.709117 .
  9. Glodzik L, Wu WE, Babb JS, Achtnichts L, Amann M, Sollberger M, Monsch AU, Gass A, Gonenb O (30 October 2012). "The whole-brain N-acetylaspartate correlates with education in normal adults". Psychiatry Research: Neuroimaging. 204 (1): 49–54. doi:10.1016/j.pscychresns.2012.04.013. PMC   3508436 . PMID   23177924.
  10. Yan HD, Ishihara K, Serikawa T, Sasa M (September 2003). "Activation by N-acetyl-L-aspartate of acutely dissociated hippocampal neurons in rats via metabotropic glutamate receptors". Epilepsia. 44 (9): 1153–9. doi: 10.1046/j.1528-1157.2003.49402.x . PMID   12919386. S2CID   39902618.

Further reading