Journal of Comparative Physiology B

, Volume 184, Issue 7, pp 835–853 | Cite as

Molecular characterization of argininosuccinate synthase and argininosuccinate lyase from the liver of the African lungfish Protopterus annectens, and their mRNA expression levels in the liver, kidney, brain and skeletal muscle during aestivation

  • You R. Chng
  • Jasmine L. Y. Ong
  • Biyun Ching
  • Xiu L. Chen
  • Wai P. Wong
  • Shit F. Chew
  • Yuen K. Ip
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Argininosuccinate synthase (Ass) and argininosuccinate lyase (Asl) are involved in arginine synthesis for various purposes. The complete cDNA coding sequences of ass and asl from the liver of Protopterus annectens consisted of 1,296 and 1,398 bp, respectively. Phylogenetic analyses revealed that the deduced Ass and Asl of P. annectens had close relationship with that of the cartilaginous fish Callorhinchus milii. Besides being strongly expressed in the liver, ass and asl expression were detectable in many tissues/organs. In the liver, mRNA expression levels of ass and asl increased significantly during the induction phase of aestivation, probably to increase arginine production to support increased urea synthesis. The increases in ass and asl mRNA expression levels during the prolonged maintenance phase and early arousal phase of aestivation could reflect increased demand on arginine for nitric oxide (NO) production in the liver. In the kidney, there was a significant decrease in ass mRNA expression level after 6 months of aestivation, indicating possible decreases in the synthesis and supply of arginine to other tissues/organs. In the brain, changes in ass and asl mRNA expression levels during the three phases of aestivation could be related to the supply of arginine for NO synthesis in response to conditions that resemble ischaemia and ischaemia–reperfusion during the maintenance and arousal phase of aestivation, respectively. The decrease in ass mRNA expression level, accompanied with decreases in the concentrations of arginine and NO, in the skeletal muscle of aestivating P. annectens might ameliorate the potential of disuse muscle atrophy.

Keywords

Ammonia toxicity Arginine Nitric oxide Nitrogen metabolism Ornithine-urea cycle Urea 
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Notes

Acknowledgments

This study was supported by the Singapore Ministry of Education through a grant (R154-000-429-112) to Y. K. Ip.

Supplementary material

360_2014_842_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 kb)

References

  1. Abu-Amara M, Yang SY, Seifalian A, Davidson B, Fuller B (2012) The nitric oxide pathway-evidence and mechanisms for protection against liver ischaemia reperfusion injury. Liver Int 32:531–543PubMedCrossRefGoogle Scholar
  2. Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615PubMedCrossRefPubMedCentralGoogle Scholar
  3. Amelio D, Garofalo F, Wong WP, Chew SF, Ip YK, Cerra MC, Tota B (2013) Nitric oxide synthase-dependent “on/off” switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle. Nitric Oxide 32:1–12PubMedCrossRefGoogle Scholar
  4. Amemiya CT, Alföldi J, Lee AP, Fan S, Philippe H, Maccallum I, Braasch I, Manousaki T, Schneider I, Rohner N, Organ C, Chalopin D, Smith JJ, Robinson M, Dorrington RA, Gerdol M, Aken B, Biscotti MA, Barucca M, Baurain D, Berlin AM, Blatch GL, Buonocore F, Burmester T, Campbell MS, Canapa A, Cannon JP, Christoffels A, De Moro G, Edkins AL, Fan L, Fausto AM, Feiner N, Forconi M, Gamieldien J, Gnerre S, Gnirke A, Goldstone JV, Haerty W, Hahn ME, Hesse U, Hoffmann S, Johnson J, Karchner SI, Kuraku S, Lara M, Levin JZ, Litman GW, Mauceli E, Miyake T, Mueller MG, Nelson DR, Nitsche A, Olmo E, Ota T, Pallavicini A, Panji S, Picone B, Ponting CP, Prohaska SJ, Przybylski D, Saha NR, Ravi V, Ribeiro FJ, Sauka-Spengler T, Scapigliati G, Searle SM, Sharpe T, Simakov O, Stadler PF, Stegeman JJ, Sumiyama K, Tabbaa D, Tafer H, Turner-Maier J, van Heusden P, White S, Williams L, Yandell M, Brinkmann H, Volff JN, Tabin CJ, Shubin N, Schartl M, Jaffe DB, Postlethwait JH, Venkatesh B, Di Palma F, Lander ES, Meyer A, Lindblad-Toh K (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature 496:311–316PubMedCrossRefPubMedCentralGoogle Scholar
  5. Ballantyne JS, Frick NT (2010) Lungfish metabolism. In: Jorgensen JM, Joss J (eds) The biology of Lungfishes. Science Publishers, New Hampshire, pp 301–335Google Scholar
  6. Beliveau Carey G, Cheung CW, Cohen NS, Brusilow S, Raijman L (1993) Regulation of urea and citrulline synthesis under physiological conditions. Biochem J 292:241–247PubMedPubMedCentralGoogle Scholar
  7. Bhaumik P, Koski MK, Bergmann U, Wierenga RK (2004) Structure determination and refinement at 2.44 Å resolution of argininosuccinate lyase from Escherichia coli. Acta Crystallogr D Biol Crystallogr 60:1964–1970PubMedCrossRefGoogle Scholar
  8. Bizzoco E, Faussone-Pellegrini MS, Vannucchi MG (2007a) Activated microglia cells express argininosuccinate synthetase and argininosuccinate lyase in the rat brain after transient ischemia. Exp Neurol 208:100–109PubMedCrossRefGoogle Scholar
  9. Bizzoco E, Vannucchi MG, Faussone-Pellegrini MS (2007b) Transient ischemia increases neuronal nitric oxide synthase, argininosuccinate synthetase and argininosuccinate lyase co-expression in rat striatal neurons. Exp Neurol 204:252–259PubMedCrossRefGoogle Scholar
  10. Booth FW, Seider MJ (1979) Early change in skeletal muscle protein synthesis after limb immobilization of rats. J Appl Physiol Respir Environ Exerc Physiol 47:974–977PubMedGoogle Scholar
  11. Braga M, Sinha Hikim AP, Datta S, Ferrini MG, Brown D, Kovacheva EL, Gonzalez-Cadavid NF, Sinha-Hikim I (2008) Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice. Apoptosis 13:822–832PubMedCrossRefGoogle Scholar
  12. Bryan NS, Grisham MB (2007) Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med 43:645–657PubMedCrossRefPubMedCentralGoogle Scholar
  13. Buck M, Chojkier M (1996) Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J 15:1753–1765PubMedPubMedCentralGoogle Scholar
  14. Carnovale CE, Ronco MT (2012) Role of nitric oxide in liver regeneration. Ann Hepatol 11:636–647PubMedGoogle Scholar
  15. Chanoine C, El Attari A, Guyot-Lenfant M, Ouedraogo L, Gallien CL (1994) Myosin isoforms and their subunits in the lungfish Protopterus annectens: changes during development and the annual cycle. J Exp Zool 269:413–421CrossRefGoogle Scholar
  16. Chew SF, Ip YK (2014) Excretory nitrogen metabolism and defence against ammonia toxicity in air-breathing fishes. J Fish Biol 84:603–638PubMedCrossRefGoogle Scholar
  17. Chew SF, Ong TF, Ho L, Tam WL, Loong AM, Hiong KC, Wong WP, Ip YK (2003) Urea synthesis in the African lungfish Protopterus dolloi: hepatic carbamoyl phosphate synthetase III and glutamine synthetase are up-regulated by 6 days of aerial exposure. J Exp Biol 206:3615–3624PubMedCrossRefGoogle Scholar
  18. Chew SF, Chan NKY, Loong AM, Hiong KC, Tam WL, Ip YK (2004) Nitrogen metabolism in the African lungfish (Protopterus dolloi) aestivating in a mucus cocoon on land. J Exp Biol 207:777–786PubMedCrossRefGoogle Scholar
  19. Chew SF, Wilson JM, Ip YK, Randall DJ (2006) Nitrogenous excretion and defense against ammonia toxicity. In: Val A, Almedia-Val V, Randall DJ (eds) The physiology of tropical fishes, fish physiology, vol 21. Academic, New York, pp 307–395CrossRefGoogle Scholar
  20. Ching B, Ong JLY, Chng YR, Chen XL, Wong WP, Chew SF, Ip YK (2014) L-gulono-γ-lactone oxidase expression and vitamin C synthesis in the brain and kidney of the African lungfish, Protopterus annectens. FASEB J. doi: 10.1096/fj.14-249508
  21. Contestabile A, Ciani E (2004) Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation. Neurochem Int 45:903–914PubMedCrossRefGoogle Scholar
  22. Corbin KD, Pendleton LC, Solomonson LP, Eichler DC (2008) Phosphorylation of argininosuccinate synthase by protein kinase A. Biochem Biophys Res Commun 377:1042–1046PubMedCrossRefGoogle Scholar
  23. De Palma C, Clementi E (2012) Nitric oxide in myogenesis and therapeutic muscle repair. Mol Neurobiol 46:682–692PubMedCrossRefGoogle Scholar
  24. Delaney RG, Lahiri S, Fishman AP (1974) Aestivation of the African lungfish Protopterus aethiopicus: cardiovascular and respiratory functions. J Exp Biol 61:111–128PubMedGoogle Scholar
  25. Delaney RG, Shub C, Fishman AP (1976) Hematologic observations on the aquatic and aestivating African lungfish Protopterus aethiopicus. Copeia 1976:423–434CrossRefGoogle Scholar
  26. Desvergne B, Michalik L, Wahli W (2006) Transcriptional regulation of metabolism. Physiol Rev 86:465–514PubMedCrossRefGoogle Scholar
  27. Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O’Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B (2011) Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat Med 17:1619–1626PubMedCrossRefPubMedCentralGoogle Scholar
  28. Fang YZ, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879PubMedCrossRefGoogle Scholar
  29. Farooqui AA (2014) Neurochemical aspects of oxidative and nitrosative stress. In: Farooqui AA (ed) Inflammation and oxidative stress in neurological disorders. Springer International Publishing, Switzerland, pp 175–206CrossRefGoogle Scholar
  30. Felsentsein J (1989) PHYLIP—phylogeny inference package (Version 3.2). Cladistics 5:164–166Google Scholar
  31. Ferreira-Cravo M, Welker AF, Hermes-Lima M (2010) The connection between oxidative stress and estivation in gastropods and anurans. Prog Mol Subcell Biol 49:47–61PubMedCrossRefGoogle Scholar
  32. Fishman AP, Pack AI, DeLaney RG, Galante RJ (1986) Estivation in Protopterus. J Morphol Suppl 190:237–248CrossRefGoogle Scholar
  33. Fitts RH, Riley DR, Widrick JJ (2001) Functional and structural adaptations of skeletal muscle to microgravity. J Exp Biol 204:3201–3208PubMedGoogle Scholar
  34. Funahashi M, Kato H, Shiosaka S, Nakagawa H (1981) Formation of arginine and guanidinoacetic acid in the kidney in vivo. Their relations with the liver and their regulation. J Biochem 89:1347–1356PubMedGoogle Scholar
  35. Gerwick L, Corley-Smith G, Bayne CJ (2007) Gene transcript changes in individual rainbow trout livers following an inflammatory stimulus. Fish Shellfish Immunol 22:157–171PubMedCrossRefGoogle Scholar
  36. Giusi G, Crudo M, Di Vito A, Facciolo RM, Garofalo F, Chew SF, Ip YK, Canonaco M (2011) Lungfish aestivating activities are locked in distinct encephalic gamma-aminobutyric acid type A receptor alpha subunits. J Neurosci Res 89:418–428PubMedCrossRefGoogle Scholar
  37. Giusi G, Zizza M, Facciolo RM, Chew SF, Ip YK, Canonaco M (2012) Aestivation and hypoxia-related events share common silent neuron trafficking processes. BMC Neurosci 13:39. doi: 10.1186/1471-2202-13-39 PubMedCrossRefPubMedCentralGoogle Scholar
  38. Guix FX, Uribesalgo I, Coma M, Muñoz FJ (2005) The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 76:126–152PubMedCrossRefGoogle Scholar
  39. Haines RJ, Pendleton LC, Eichler DC (2011) Argininosuccinate synthase: at the center of arginine metabolism. Int J Biochem Mol Biol 2:8–23PubMedPubMedCentralGoogle Scholar
  40. Haines RJ, Corbin KD, Pendleton LC, Eichler DC (2012) Protein kinase C alpha phosphorylates a novel argininosuccinate synthase site at serine 328 during calcium-dependent stimulation of endothelial nitric-oxide synthase in vascular endothelial cells. J Biol Chem 287:26168–26176PubMedCrossRefPubMedCentralGoogle Scholar
  41. Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98Google Scholar
  42. Hao G, Xie L, Gross SS (2004) Argininosuccinate synthetase is reversibly inactivated by S-nitrosylation in vitro and in vivo. J Biol Chem 279:36192–36200PubMedCrossRefGoogle Scholar
  43. Hermes-Lima M, Storey KB (1995) Antioxidant defenses and metabolic depression in a pulmonate land snail. Am J Physiol 268:R1386–R1393PubMedGoogle Scholar
  44. Hermes-Lima M, Zenteno-Savin T (2002) Animal response to drastic changes in oxygen availability and physiological oxidative stress. Comp Biochem Physiol C 133:537–556CrossRefGoogle Scholar
  45. Hiong KC, Ip YK, Wong WP, Chew SF (2013) Differential gene expression in the brain of the African lungfish, Protopterus annectens, after six days or six months of aestivation in air. PLoS One 8:e71205. doi: 10.1371/journal.pone.0071205 PubMedCrossRefPubMedCentralGoogle Scholar
  46. Hiong KC, Ip YK, Wong WP, Chew SF (2014) Brain Na+/K+-ATPase alpha-subunit isoforms and aestivation in the African lungfish, Protopterus annectens. J Comp Physiol B 184:571–587Google Scholar
  47. Huang CW, Chen YH, Chen YH, Tsai YC, Lee HJ (2009) The interaction of Glu294 at the subunit interface is important for the activity and stability of goose delta-crystallin. Mol Vis 15:2358–2363PubMedPubMedCentralGoogle Scholar
  48. Husson A, Brasse-Lagnel C, Fairand A, Renouf S, Lavoinne A (2003) Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem 270:1887–1899PubMedCrossRefGoogle Scholar
  49. Icardo JM, Loong AM, Colvee E, Wong WP, Ip YK (2012) The alimentary canal of the African lungfish Protopterus annectens during aestivation and after arousal. Anat Rec (Hoboken) 295:60–72CrossRefGoogle Scholar
  50. Iftikar FI, Patel M, Ip YK, Wood CM (2007) The influence of feeding on aerial and aquatic oxygen consumption, nitrogenous waste excretion, and metabolic fuel usage in the African lungfish, Protopterus annectens. Can J Zool 86:790–800CrossRefGoogle Scholar
  51. Ip YK, Chew SF (2010a) Nitrogen metabolism and excretion during aestivation. In: Navas CA, Carvalho JE (eds) Aestivation: molecular and physiological aspects, progress in molecular and subcellular biology. Springer, Heidelberg, pp 63–93CrossRefGoogle Scholar
  52. Ip YK, Chew SF (2010b) Ammonia production, excretion, toxicity, and defense in fish: a review. Front Physiol 1:134. doi: 10.3389/fphys.2010.00134 PubMedCrossRefPubMedCentralGoogle Scholar
  53. Ip YK, Peh BK, Tam WL, Wong WP, Chew SF (2005a) Effects of intra-peritoneal injection with NH4Cl, urea, or NH4Cl+ urea on nitrogen excretion and metabolism in the African lungfish Protopterus dolloi. J Exp Zool A 303:272–282CrossRefGoogle Scholar
  54. Ip YK, Yeo PJ, Loong AM, Hiong KC, Wong WP, Chew SF (2005b) The interplay of increased urea synthesis and reduced ammonia production in the African lungfish Protopterus aethiopicus during 46 days of aestivation in a mucus cocoon. J Exp Zool A 303:1054–1065CrossRefGoogle Scholar
  55. Jackson MJ (2013) Interactions between reactive oxygen species generated by contractile activity and aging in skeletal muscle? Antioxid Redox Signal 19:804–812PubMedCrossRefPubMedCentralGoogle Scholar
  56. Janssens PA (1964) The metabolism of the aestivating African lungfish. Comp Biochem Physiol 11:105–117PubMedCrossRefGoogle Scholar
  57. Kaminski HJ, Andrade FH (2001) Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscul Disord 11:517–524PubMedCrossRefGoogle Scholar
  58. Karlberg T, Collins R, van den Berg S, Flores A, Hammarström M, Högbom M, Holmberg Schiavone L, Uppenberg J (2008) Structure of human argininosuccinate synthetase. Acta Crystallogr D Biol Crystallogr 64:279–286PubMedCrossRefGoogle Scholar
  59. Laberge T, Walsh PJ (2011) Phylogenetic aspects of carbamoyl phosphate synthetase in lungfish: a transitional enzyme in transitional fishes. Comp Biochem Physiol Part D Genomics Proteomics 6:187–194PubMedCrossRefGoogle Scholar
  60. Lahiri S, Szidon JP, Fishman AP (1970) Potential respiratory and circulatory adjustments to hypoxia in the African lungfish. Fed Proc 29:1141–1148PubMedGoogle Scholar
  61. Lemke CT, Howell PL (2001) The 1.6 Å crystal structure of E. coli argininosuccinate synthetase suggests a conformational change during catalysis. Structure 9:1153–1164PubMedCrossRefGoogle Scholar
  62. Levillain O (2012) Expression and function of arginine-producing and consuming-enzymes in the kidney. Amino Acids 42:1237–1252PubMedCrossRefGoogle Scholar
  63. Lim CK, Wong WP, Lee SML, Chew SF, Ip YK (2004) The ammonotelic African lungfish, Protopterus dolloi, increases the rate of urea synthesis and becomes ureotelic after feeding. J Comp Physiol B 174:555–564PubMedGoogle Scholar
  64. Loong AM, Hiong KC, Lee SM, Wong WP, Chew SF, Ip YK (2005) Ornithine-urea cycle and urea synthesis in African lungfishes, Protopterus aethiopicus and Protopterus annectens, exposed to terrestrial conditions for six days. J Exp Zool A 303:354–365CrossRefGoogle Scholar
  65. Loong AM, Ang SF, Wong WP, Poertner HO, Bock C, Wittig R, Bridges CR, Chew SF, Ip YK (2008a) Effects of hypoxia on the energy status and nitrogen metabolism of African lungfish during aestivation in a mucus cocoon. J Comp Physiol B 178:853–865PubMedCrossRefGoogle Scholar
  66. Loong AM, Pang CY, Hiong KC, Wong WP, Chew SF, Ip YK (2008b) Increased urea synthesis and/or suppressed ammonia production in the African lungfish, Protopterus annectens, during aestivation in air or mud. J Comp Physiol B 178:351–363PubMedCrossRefGoogle Scholar
  67. Loong AM, Chng YR, Chew SF, Wong WP, Ip YK (2012a) Molecular characterization and mRNA expression of carbamoyl phosphate synthetase III in the liver of the African lungfish, Protopterus annectens, during aestivation or exposure to ammonia. J Comp Physiol B 182:367–379PubMedCrossRefGoogle Scholar
  68. Loong AM, Hiong KC, Wong WP, Chew SF, Ip YK (2012b) Differential gene expression in the liver of the African lungfish, Protopterus annectens, after 6 days of estivation in air. J Comp Physiol B 182:231–245PubMedCrossRefGoogle Scholar
  69. Mori M, Gotoh T (2004) Arginine metabolic enzymes, nitric oxide and infection. J Nutr 134:2820S–2825S discussion 2853SPubMedGoogle Scholar
  70. Morris SM Jr (1992) Regulation of enzymes of urea and arginine synthesis. Annu Rev Nutr 12:81–101PubMedCrossRefGoogle Scholar
  71. Morris SM Jr (2002) Regulation of enzymes of the urea cycle and arginine metabolism. Annu Rev Nutr 22:87–105PubMedCrossRefGoogle Scholar
  72. Morris SM Jr, Moncman CL, Rand KD, Dizikes GJ, Cederbaum SD, O’Brien WE (1987) Regulation of mRNA levels for five urea cycle enzymes in rat liver by diet, cyclic AMP, and glucocorticoids. Arch Biochem Biophys 256:343–353PubMedCrossRefGoogle Scholar
  73. Morris SM Jr, Moncman CL, Holub JS, Hod Y (1989) Nutritional and hormonal regulation of mRNA abundance for arginine biosynthetic enzymes in kidney. Arch Biochem Biophys 273:230–237PubMedCrossRefGoogle Scholar
  74. Moshage H, Kok B, Huizenga JR, Jansen PL (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 41:892–896PubMedGoogle Scholar
  75. O’Brien WE (1979) Isolation and characterization of argininosuccinate synthetase from human liver. Biochemistry 18:5353–5356PubMedCrossRefGoogle Scholar
  76. O’Brien WE, Barr RH (1981) Argininosuccinate lyase: purification and characterization from human liver. Biochemistry 20:2056–2060PubMedCrossRefGoogle Scholar
  77. Ojeda JL, Wong WP, Ip YK, Icardo JM (2008) Renal corpuscle of the African lungfish Protopterus dolloi: structural and histochemical modifications during aestivation. Anat Rec (Hoboken) 291:1156–1172CrossRefGoogle Scholar
  78. Pye D, Palomero J, Kabayo T, Jackson MJ (2007) Real-time measurement of nitric oxide in single mature mouse skeletal muscle fibres during contractions. J Physiol 581:309–318PubMedCrossRefPubMedCentralGoogle Scholar
  79. Ramamoorthy S, Donohue M, Buck M (2009) Decreased Jun-D and myogenin expression in muscle wasting of human cachexia. Am J Physiol Endocrinol Metab 297:E392–E401PubMedCrossRefPubMedCentralGoogle Scholar
  80. Rice ME, Lee EJ, Choy Y (1995) High levels of ascorbic acid, not glutathione, in the CNS of anoxia-tolerant reptiles contrasted with levels in anoxia-intolerant species. J Neurochem 64:1790–1799PubMedCrossRefGoogle Scholar
  81. Sampaleanu LM, Vallée F, Thompson GD, Howell PL (2001) Three-dimensional structure of the argininosuccinate lyase frequently complementing allele Q286R. Biochemistry 40:15570–15580PubMedCrossRefGoogle Scholar
  82. Smith HW (1930) Metabolism of the lungfish Protopterus aethiopicus. J Biol Chem 88:97–130Google Scholar
  83. Tesmer JJ, Klem TJ, Deras ML, Davisson VJ, Smith JL (1996) The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families. Nat Struct Biol 3:74–86PubMedCrossRefGoogle Scholar
  84. Thomason DB, Biggs RB, Booth FW (1989) Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle. Am J Physiol 257:300–305Google Scholar
  85. Virarkar M, Alappat L, Bradford PG, Awad AB (2013) l-arginine and nitric oxide in CNS function and neurodegenerative diseases. Crit Rev Food Sci Nutr 53:1157–1167PubMedCrossRefGoogle Scholar
  86. Westerblad H, Allen DG (2011) Emerging roles of ROS/RNS in muscle function and fatigue. Antioxid Redox Signal 15:2487–2499PubMedCrossRefGoogle Scholar
  87. Wiesinger H (2001) Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 64:365–391PubMedCrossRefGoogle Scholar
  88. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17Google Scholar
  89. Yu B, Howell PL (2000) Intragenic complementation and the structure and function of argininosuccinate lyase. Cell Mol Life Sci 57:1637–1651PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • You R. Chng
    • 1
  • Jasmine L. Y. Ong
    • 1
  • Biyun Ching
    • 1
  • Xiu L. Chen
    • 1
  • Wai P. Wong
    • 1
  • Shit F. Chew
    • 2
  • Yuen K. Ip
    • 1
  1. 1.Department of Biological SciencesNational University of SingaporeSingaporeRepublic of Singapore
  2. 2.Natural Sciences and Science Education, National Institute of EducationNanyang Technological UniversitySingaporeRepublic of Singapore

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