Ubiquitous presence of argininosuccinate at millimolar levels in the central nervous system of Aplysia californica. 2007

Xiaoying Ye, and Won-Suk Kim, and Stanislav S Rubakhin, and Jonathan V Sweedler
Department of Chemistry and the Beckman Institute, University of Illinois, Urbana, Illinois 61801, USA.

Endogenous nitric oxide (NO) is generated by nitric oxide synthases (NOSs), which convert arginine (Arg) and oxygen to citrulline (Cit) and NO. Cit can be enzymatically transformed back to Arg by argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via a pathway involving argininosuccinate (ArgSuc). Arg, Cit, and ArgSuc levels have been measured in single neurons, neuronal clusters, and neuropil from the nervous system of the common neurobiological model Aplysia californica. Using capillary electrophoresis with laser-induced fluorescence detection, ArgSuc was found to be present in the nervous system in millimolar concentrations at levels significantly exceeding Cit levels (p<0.01). ArgSuc levels are proportional to Arg concentrations in single neurons, whereas they have no clear correlation to the Cit or Arg/Cit ratio. NOS-expressing neurons often exhibit fixative-resistant nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining. Incubation of ganglia with Arg results in an increase in Cit and ArgSuc levels in the NADPH-d-positive neuropil with no effect on ArgSuc levels in NADPH-d-negative neurons, suggesting NOS activity in the neuropil. Similar incubation with Cit leads to decreased ArgSuc levels in NADPH-d-negative neurons. These results can be explained by localization of NOS and ASS in different neurons; therefore, the complete Arg-Cit-NO cycle may not be present in the same neuron. The surprisingly high intracellular ArgSuc concentration suggests alternative sources of ArgSuc and that at least a portion may be formed by the reverse reaction of ASL (catalyzing the conversion of Arg to ArgSuc), which can be inhibited by Cit.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009415 Nerve Net A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction. Neural Networks (Anatomic),Nerve Nets,Net, Nerve,Nets, Nerve,Network, Neural (Anatomic),Networks, Neural (Anatomic),Neural Network (Anatomic)
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002490 Central Nervous System The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D002956 Citrulline
D006458 Hemolymph The blood/lymphlike nutrient fluid of some invertebrates. Hemolymphs
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001048 Aplysia An opisthobranch mollusk of the order Anaspidea. It is used frequently in studies of nervous system development because of its large identifiable neurons. Aplysiatoxin and its derivatives are not biosynthesized by Aplysia, but acquired by ingestion of Lyngbya (seaweed) species. Aplysias
D001120 Arginine An essential amino acid that is physiologically active in the L-form. Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D001125 Argininosuccinic Acid This amino acid is formed during the urea cycle from citrulline, aspartate and ATP. This reaction is catalyzed by argininosuccinic acid synthetase. N-(4-Amino-4-carboxybutyl)amidino-L-aspartic Acid,Acid, Argininosuccinic

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