New Radioisotopic Assays of Argininosuccinate Synthetase and Argininosuccinase12

Kobayashi, Hideo; Oyamada, Ikuko; Mizutani-Funahashi, Masumi; Nakagawa, Hachiro

doi:10.1093/oxfordjournals.jbchem.a131162

Cited by 29 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was established many years ago that ASS activity was present in many tissues with the highest values found in the liver and kidneys [10,11], and this was confirmed recently at both mRNA and protein levels [12]. Concerning such a repartition and as illustrated in Fig.…”

Section: Ass a Ubiquitous Enzymementioning

confidence: 71%

Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle

Husson¹,

Brasse‐Lagnel²,

Fairand³

et al. 2003

European Journal of Biochemistry

276

239

View full text Add to dashboard Cite

Argininosuccinate synthetase (ASS, EC 6.3.4.5) catalyses the condensation of citrulline and aspartate to form argininosuccinate, the immediate precursor of arginine. First identified in the liver as the limiting enzyme of the urea cycle, ASS is now recognized as a ubiquitous enzyme in mammalian tissues. Indeed, discovery of the citrulline–NO cycle has increased interest in this enzyme that was found to represent a potential limiting step in NO synthesis. Depending on arginine utilization, location and regulation of ASS are quite different. In the liver, where arginine is hydrolyzed to form urea and ornithine, the ASS gene is highly expressed, and hormones and nutrients constitute the major regulating factors: (a) glucocorticoids, glucagon and insulin, particularly, control the expression of this gene both during development and adult life; (b) dietary protein intake stimulates ASS gene expression, with a particular efficiency of specific amino acids like glutamine. In contrast, in NO‐producing cells, where arginine is the direct substrate in the NO synthesis, ASS gene is expressed at a low level and in this way, proinflammatory signals constitute the main factors of regulation of the gene expression. In most cases, regulation of ASS gene expression is exerted at a transcriptional level, but molecular mechanisms are still poorly understood.

show abstract

Section: Ass a Ubiquitous Enzymementioning

confidence: 71%

Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle

Husson¹,

Brasse‐Lagnel²,

Fairand³

et al. 2003

European Journal of Biochemistry

276

239

View full text Add to dashboard Cite

show abstract

“…4 for a review). However, other tissues and cell types also contain low levels of argininosuccinate synthetase (AS) and argininosuccinate lyase (AL), which together synthesize arginine from citrulline (5)(6)(7)(8). Therefore, arginine can be generated from citrulline which is produced as a co-product of the NOS reaction, forming a cycle which could be termed the "citrulline-NO cycle" (9) or "arginine-citrulline cycle" (10).…”

mentioning

confidence: 99%

Coinduction of Nitric Oxide Synthase, Argininosuccinate Synthetase, and Argininosuccinate Lyase in Lipopolysaccharide-treated Rats

Nagasaki

Gotoh

Takeya

et al. 1996

Journal of Biological Chemistry

121

View full text Add to dashboard Cite

Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase (NOS), and citrulline which is generated can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). Rats were injected with bacterial lipopolysaccharide (LPS), and expression of the inducible isoform of NOS (iNOS), AS, and AL was analyzed. In RNA blot analysis, iNOS mRNA was undetectable before the LPS treatment but was induced by LPS in the lung, heart, liver, and spleen, and less strongly in the skeletal muscle and testis. AS mRNA was induced in the lung and spleen, and AL mRNA was weakly induced in these tissues. AS and AL mRNAs were abundant in the control liver and remained unchanged after the treatment. Kinetic studies showed that iNOS mRNA increased rapidly in both spleen and lung, reached a maximum 2-5 h after the treatment, and decreased thereafter. On the other hand, AS mRNA increased more slowly and reached a maximum in 6 -12 h (by about 10-fold in the spleen and 2-fold in the lung). AL mRNA in the spleen and lung increased slowly and remained high up to 24 h. In immunoblot analysis, increase of iNOS protein was evident in the lung, liver, and spleen, and there was an increase of AS protein in the lung and spleen. In immunohistochemical analysis, macrophages in the spleen that were negative for iNOS and AS before LPS treatment were strongly positive for both iNOS and AS after this treatment. As iNOS, AS, and AL were coinduced in rat tissues and cells, citrulline-arginine recycling seems to be important in NO synthesis under the conditions of stimulation.Nitric oxide (NO) is a major messenger molecule regulating blood vessel dilatation and immune function and functions as a neurotransmitter in the brain and peripheral nervous system (see Refs. 1-3 for reviews). NO is synthesized from arginine by nitric oxide synthase (NOS), 1 generating citrulline as another product. Cellular NO production is absolutely dependent on availability of arginine. This amino acid can be obtained from exogenous sources via the blood circulation, from intracellular protein degradation, or by endogenous synthesis of arginine.Major sites of arginine synthesis in ureotelic animals are the liver, where arginine generated in the urea cycle (ornithine cycle) is rapidly converted to urea and ornithine by arginase, and the kidney, where arginine is synthesized from citrulline and released into the blood circulation (see Ref. 4 for a review). However, other tissues and cell types also contain low levels of argininosuccinate synthetase (AS) and argininosuccinate lyase (AL), which together synthesize arginine from citrulline (5-8). Therefore, arginine can be generated from citrulline which is produced as a co-product of the NOS reaction, forming a cycle which could be termed the "citrulline-NO cycle" (9) or "arginine-citrulline cycle" (10). Vascular endothelial cells can convert citrulline to arginine (11), and this conversion is increased when cells are stimulated to produce NO (12). Cytokine-activated macrophages, which produ...

show abstract

“…In addition, Arg is used for the synthesis of proteins and peptides, creatine, agmatine and the synthesis of polyamines. Although the CNS contains arginase, ASL, and ASS, it lacks ornithine transcarbamylase 2–5. In consequence, citrulline, whose presence in the CNS has been known for a long time, derives mainly from NO synthesis, via NO synthase (NOS) activity.…”

Section: The Importance Of the Glial‐neuronal Transfer Of Arginine Inmentioning

confidence: 99%

Glial‐Neuronal Transfer of Arginine and S‐Nitrosothiols in Nitric Oxide Transmission

Grima

Benz

et al. 2002

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

The arginine-nitric oxide (Arg-NO) and the S-nitrosothiols systems, two less well-studied aspects of NO transmission in the central nervous system, are reviewed. A growing body of evidence suggested that they play a crucial role in NO synthesis and activity. l-Arginine, the NO precursor, is predominantly localized in glia. Together with in vitro and in vivo results of arginine release, this suggests a transfer of arginine from glia to neurons in order to supply NO synthase with its substrate. NO biosynthesis may thus involve the co-occurrence of the glial-neuronal transfer of arginine and of NOS activation. The arginine availability may shed light on the dual, beneficial and toxic effects of NO. At low arginine concentrations, neuronal NO synthase generates NO and superoxide, favouring the production of the toxin peroxynitrite. NMDA-induced excitotoxicity in neuronal cells is dependent on arginine availability and glia may play a neuroprotective role by supplying arginine. The reversible S-nitros(yl)ation of thiol containing molecules may represent an important cellular signal transduction mechanism, probably comparable to phosphorylation. S-nitrosothiols, in particular through the presence and release of S-nitroso-cysteinylglycine in sensory thalamus, may act as a local buffering system in NO transmission. This may represent a novel specific facilitating mechanism in order to enhance transmission of persistent stimuli.

show abstract

New Radioisotopic Assays of Argininosuccinate Synthetase and Argininosuccinase12

Cited by 29 publications

References 0 publications

Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle

Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle

Coinduction of Nitric Oxide Synthase, Argininosuccinate Synthetase, and Argininosuccinate Lyase in Lipopolysaccharide-treated Rats

Glial‐Neuronal Transfer of Arginine and S‐Nitrosothiols in Nitric Oxide Transmission

Contact Info

Product

Resources

About