A Gas Chromatographic Method for the Determination of N‐Acetyl‐<scp>l</scp>‐Aspartic Acid, N‐Acetyl‐α‐ Aspartylglutamic Acid and β‐Citryl‐<scp>l</scp>‐Glutamic Acid and Their Distributions in the Brain and Other Organs of Various Species of Animals

Miyake, Masaham; Kawaguchi, Yasuo; Sorimachi, Masaru

doi:10.1111/j.1471-4159.1981.tb01665.x

Cited by 183 publications

(96 citation statements)

References 16 publications

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“…This is consistent with the finding that the genes that surround the chicken RIMKL gene are homologous to those that surround the mammalian RIMKLB gene, whereas the genetic environment of the RIMKLA gene is completely different (not shown). The ancestral form of RIMKLA and RIMKLB had presumably both activities, consistent with the presence of both NAAG and ␤-citrylglutamate in fishes (29). The finding that the NAAG/NAA ratio in fish CNS is much lower than in mammals or amphibians (26,29) suggests, however, that the fish enzyme is not very good at synthesizing NAAG.…”

Section: Agreement With Previous Results Suggesting That Naag Ismentioning

confidence: 67%

“…The ancestral form of RIMKLA and RIMKLB had presumably both activities, consistent with the presence of both NAAG and ␤-citrylglutamate in fishes (29). The finding that the NAAG/NAA ratio in fish CNS is much lower than in mammals or amphibians (26,29) suggests, however, that the fish enzyme is not very good at synthesizing NAAG.…”

Section: Agreement With Previous Results Suggesting That Naag Ismentioning

confidence: 67%

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Molecular Identification of N-Acetylaspartylglutamate Synthase and β-Citrylglutamate Synthase

Collard

Stroobant

Lamosa

et al. 2010

Journal of Biological Chemistry

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The purpose of the present work was to determine the identity of the enzymes that synthesize N-acetylaspartylglutamate (NAAG), the most abundant dipeptide present in vertebrate central nervous system (CNS), and ␤-citrylglutamate, a structural analogue of NAAG present in testis and immature brain. Previous evidence suggests that NAAG is not synthesized on ribosomes but presumably is synthesized by a ligase. As attempts to detect this ligase in brain extracts failed, we searched the mammalian genomes for putative enzymes that could catalyze this type of reaction. Mammalian genomes were found to encode two putative ligases homologous to Escherichia coli RIMK, which ligates glutamates to the C terminus of ribosomal protein S6. One of them, named RIMKLA, is almost exclusively expressed in the CNS, whereas RIMKLB, which shares 65% sequence identity with RIMKLA, is expressed in CNS and testis. Both proteins were expressed in bacteria or HEK293T cells and purified. RIMKLA catalyzed the ATP-dependent synthesis of N-acetylaspartylglutamate from N-acetylaspartate and L-glutamate. RIMKLB catalyzed this reaction as well as the synthesis of ␤-citrylglutamate. The nature of the reaction products was confirmed by mass spectrometry and NMR. RIMKLA was shown to produce stoichiometric amounts of NAAG and ADP, in agreement with its belonging to the ATP-grasp family of ligases. The molecular identification of these two enzymes will facilitate progress in the understanding of the function of NAAG and ␤-citrylglutamate. N-Acetylaspartylglutamate (NAAG),3 the most abundant dipeptide in the CNS, is present in brain and in the spinal cord, most particularly in neurons of the anterior horn (1). NAAG can be released from neurons upon calcium depolarization (reviewed in Ref. 1) and is a substrate for two glial peptidases, glutamate carboxypeptidase-II (2) and, to a lower extent, glutamate carboxypeptidase-III (3), which are anchored to the plasma membrane with their catalytic site oriented toward the outside of the cell. NAAG long has been thought to be a neurotransmitter able to bind to the metabotropic glutamate receptors mGluR3 (4). Two recent reports suggest, however, that the effects of NAAG as a neurotransmitter are due to a 0.5% glutamate contamination present in commercial NAAG (5, 6). The function of NAAG is, therefore, presently unknown.␤-Citrylglutamate (BCG), which is structurally close to NAAG, is less well characterized. It was first identified in newborn rat brain, where its concentration reaches 0.5-1 mol/g at birth and then decreases with age (7). BCG also was detected in kidneys and heart and to a much lower extent in intestine, spinal cord, and lung of newborn rats. The content of BCG in all organs decreased with age to the noticeable exception of testes, where its concentration increases during sexual maturation and remains constant in adulthood (8,9). BCG is present not only in the testes of mammals but also in those of amphibians and fishes. There is evidence in germinal cells for a role in spermatogenesis (9). BCG rec...

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Section: Agreement With Previous Results Suggesting That Naag Ismentioning

confidence: 67%

Section: Agreement With Previous Results Suggesting That Naag Ismentioning

confidence: 67%

Molecular Identification of N-Acetylaspartylglutamate Synthase and β-Citrylglutamate Synthase

Collard

Stroobant

Lamosa

et al. 2010

Journal of Biological Chemistry

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“…It is interesting to note that the expression of the neuronal dipeptide NAAG also exhibits an increasing concentration gradient from the rostral to the caudal CNS. NAA has not been reported to exhibit such an increasing concentration gradient , and in fact may have an opposite distribution pattern, with higher levels in forebrain, and lower levels in the hindbrain and spinal cord of adult animals (Miyake et al, 1981;Tallan, 1957).…”

Section: Naa Synthesismentioning

confidence: 99%

“…The levels found in various areas of the brain can reach 10mM or greater (Bluml, 1999;Miyake et al, 1981;Pan and Takahashi, 2005), making it one of the most concentrated molecules in the CNS. After five decades of research by neuroscientists and clinicians into the roles played by NAA, its metabolic and neurochemical functions remain controversial, and its connections to several disease states are uncertain.…”

Section: Introductionmentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

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1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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“…[1][2][3] In addition, b-CG was found in not only the brain of neonatal rats but also the testis and lens of adult rats. 4,5) This compound appeared at high concentrations during the period characterized by growth and differentiation of neurons, spermatozoa and lens-fibercells in each tissue.…”

mentioning

confidence: 97%

cDNA Cloning of the Sry-Related Gene Sox6 from Rat with Tissue-Specific Expression.

Narahara

Yamada

Hamada-Kanazawa

et al. 2002

Biological & Pharmaceutical Bulletin

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Previously, we isolated a novel compound from the neonatal rat brain and identified it as b-citryl-L-glutamate (b-CG). [1][2][3] In addition, b-CG was found in not only the brain of neonatal rats but also the testis and lens of adult rats. 4,5) This compound appeared at high concentrations during the period characterized by growth and differentiation of neurons, spermatozoa and lens-fibercells in each tissue. [4][5][6][7] Recently, we found two facts. 1. b-CG was localized exclusively in the primary cultured neurons 6) and in the neurons which differentiated from retinoic acid-treated P19 cells.8) P19 is a cell line derived from mouse embrional carcinomas (EC). 9) 2. The concentration of b-CG increased significantly with the differentiation of P19 cells into neurons.8) b-CG may play important roles in the growth and differentiation in the brain, testis and lens. However, the functional roles of b-CG are unclear.While, SRY, a candidate gene responsible for testis determination, has been isolated from the sex determining regions of human and mouse Y chromosome.10,11) SRY encodes a protein with a DNA-binding motif known as the high-mobility-group (HMG) box. 10,11) In addition to SRY, genes encoding an SRY-type HMG box (SOX genes/sox) have been identified by polymerase chain reaction (PCR) with primers based on the conserved amino acid sequence of the HMG boxes of mammalian SRY. [12][13][14][15][16][17][18] No less than 30 types of SOX gene have been isolated from humans, 19) mice and rainbow trout, and they have been considered to be related to the regulation of cell differentiation and to the differentiation pattern. 17,[20][21][22][23] Sox6 showed the characteristic expression pattern and distribution among the sox family and it was specifically expressed during cell differentiation in tissues including the immature brain and adult testis. 24,25) The developmental changes in the brain or testis and tissues distributions of Sox6 were markedly similar to those of b-CG studied by us.2-4) Therefore, we have the interest for the relationship between Sox6 and b-CG.Sox6 has been cloned only in mice, 25) human 26) and rainbow trout, 24) and thought to function as a transcriptional regulation factor. Sox6 was preferentially expressed, when 3 kinds of cells including nerve cell, spermatide and the optic vesicle cell differentiated, and b-CG in these cells also remarkably increased in the same time. However the developmental changes and distributions of b-CG have been mainly examined in rats.2-4) So, we intended to examine the cloning of the Sox6 gene from rat and the distributions of rSox6 (rat Sox6) mRNA. In this study, rSox6 cDNA was cloned by PCR with primers based on the mSox6 (mouse Sox6) cDNA from the adult rat testis cDNA library. The organ distribution and the developmental changes were examined by Northern blotting and a Real-time quantitative reverse transcription (RT)-PCR method. MATERIALS AND METHOD MaterialsThe SuperScript cloning system and Escherichia coli DH5a competent cells were obtained from GIBCO/BRL an...

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A Gas Chromatographic Method for the Determination of N‐Acetyl‐l‐Aspartic Acid, N‐Acetyl‐α‐ Aspartylglutamic Acid and β‐Citryl‐l‐Glutamic Acid and Their Distributions in the Brain and Other Organs of Various Species of Animals

Cited by 183 publications

References 16 publications

Molecular Identification of N-Acetylaspartylglutamate Synthase and β-Citrylglutamate Synthase

Molecular Identification of N-Acetylaspartylglutamate Synthase and β-Citrylglutamate Synthase

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

cDNA Cloning of the Sry-Related Gene Sox6 from Rat with Tissue-Specific Expression.

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