Argininosuccinate synthase: At the center of arginine metabolism

International Journal of Biochemistry and Molecular Biology

Volumn 2, Issue 1, 2011, Pages 8-23

  Haines, Ricci J ^a   Pendleton, Laura C ^a   Eichler, Duane C ^a  

^a UNIVERSITY OF SOUTH FLORIDA   (United States)

Author keywords

Arginase; Arginine metabolism; Arginine recycling; Argininosuccinate synthase; Nitric oxide; Urea cycle

Indexed keywords

ARGININE; ARGININOSUCCINATE SYNTHASE; CREATININE; CYCLIC AMP;

AMINO ACID BLOOD LEVEL; BIOSYNTHESIS; CELLULAR DISTRIBUTION; CITRULLINEMIA; CITRULLINEMIA TYPE II; CYTOPLASM; ENZYME LOCALIZATION; ENZYME METABOLISM; GENE MUTATION; HUMAN; LIVER CELL CARCINOMA; MITOCHONDRIAL MEMBRANE; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; TRANSCRIPTION REGULATION; UREA CYCLE;

EID: 79952151320     PISSN: None     EISSN: 21524114     Source Type: Journal    
DOI: None     Document Type: Review

References (107)

1. Morris SM, Jr. Regulation of enzymes of the urea cycle and arginine metabolism. Annu Rev Nutr 2002; 22: 87-105.
2. Forstermann U and Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006; 113: 1708-1714.
3. Flam BR, Hartmann PJ, Harrell-Booth M, Solomonson LP and Eichler DC. Caveolar localization of arginine regeneration enzymes, argininosuccinate synthase, and lyase, with endothelial nitric oxide synthase. Nitric Oxide 2001; 5: 187-197.
4. Fulton D, Babbitt R, Zoellner S, Fontana J, Acevedo L, McCabe TJ, Iwakiri Y and Sessa WC. Targeting of endothelial nitric-oxide synthase to the cytoplasmic face of the Golgi complex or plasma membrane regulates Akt- versus calcium- dependent mechanisms for nitric oxide release. J Biol Chem 2004; 279: 30349-30357.
5. Cohen NS and Kuda A. Argininosuccinate synthetase and argininosuccinate lyase are localized around mitochondria: an immunocytochemical study. J Cell Biochem 1996; 60: 334-340.
6. Stubbs M and Gibbons G. Hans Adolf Krebs (1900-1981) his life and times. IUBMB Life 2000; 50: 163-166.
7. Meijer AJ, Lamers WH and Chamuleau RA. Nitrogen metabolism and ornithine cycle function. Physiol Rev 1990; 70: 701-748.
8. Ratner S. Enzymes of arginine and urea synthesis. Adv Enzymol Relat Areas Mol Biol 1973; 39: 1-90.
9. Davis PK and Wu G. Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes. Comp Biochem Physiol B Biochem Mol Biol 1998; 119: 527-537.
10. Cheung CW, Cohen NS and Raijman L. Channeling of urea cycle intermediates in situ in permeabilized hepatocytes. J Biol Chem 1989; 264: 4038-4044.
11. Watford M. Channeling in the urea cycle: a metabolon spanning two compartments. Trends Biochem Sci 1989; 14: 313-314.
12. Gao HZ, Kobayashi K, Tabata A, Tsuge H, Iijima M, Yasuda T, Kalkanoglu HS, Dursun A, Tokatli A, Coskun T, Trefz FK, Skladal D, Mandel H, Seidel J, Kodama S, Shirane S, Ichida T, Makino S, Yoshino M, Kang JH, Mizuguchi M, Barshop BA, Fuchinoue S, Seneca S, Zeesman S, Knerr I, Rodes M, Wasant P, Yoshida I, De Meirleir L, Abdul Jalil M, Begum L, Horiuchi M, Katunuma N, Nakagawa S and Saheki T. Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients. Hum Mutat 2003; 22: 24-34.
13. Saheki T, Kobayashi K, Iijima M, Horiuchi M, Begum L, Jalil MA, Li MX, Lu YB, Ushikai M, Tabata A, Moriyama M, Hsiao KJ and Yang Y. Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab 2004; 81 Suppl 1: S20-26.
14. Kobayashi K, Sinasac DS, Iijima M, Boright AP, Begum L, Lee JR, Yasuda T, Ikeda S, Hirano R, Terazono H, Crackower MA, Kondo I, Tsui LC, Scherer SW and Saheki T. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet 1999; 22: 159-163.
15. Cohen NS, Cheung CW and Raijman L. Channeling of extramitochondrial ornithine to matrix ornithine transcarbamylase. J Biol Chem 1987; 262: 203-208.
16. Powers-Lee SG, Mastico RA and Bendayan M. The interaction of rat liver carbamoyl phosphate synthetase and ornithine transcarbamoylase with inner mitochondrial membranes. J Biol Chem 1987; 262: 15683-15688.
17. White MF, Gazzola GC and Christensen HN. Cationic amino acid transport into cultured animal cells. I. Influx into cultured human fibroblasts. J Biol Chem 1982; 257: 4443-4449.
18. Maher AD, Kuchel PW, Ortega F, de Atauri P, Centelles J and Cascante M. Mathematical modelling of the urea cycle. A numerical investigation into substrate channelling. Eur J Biochem 2003; 270: 3953-3961.
19. Panza JA, Garcia CE, Kilcoyne CM, Quyyumi AA and Cannon RO, 3rd. Impaired endotheliumdependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. Circulation 1995; 91: 1732-1738.
20. Prins HA, Houdijk AP, van Lambalgen AA, Teerlink T, Meijer S, Thijs LG and van Leeuwen PA. Paradoxical changes in organ blood flow after arginase infusion in the non-stressed rat. Shock 1998; 9: 422-427.
21. Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA and Morris SM, Jr. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 2004; 170: 148-153.
22. Langle F, Roth E, Steininger R, Winkler S and Muhlbacher F. Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions. Transplantation 1995; 59: 1542-1549.
23. Morris SM, Jr. Arginine metabolism: boundaries of our knowledge. J Nutr 2007; 137: 1602S-1609S.
24. Morris SM, Jr. Regulation of enzymes of urea and arginine synthesis. Annu Rev Nutr 1992; 12: 81-101.
25. Beliveau Carey G, Cheung CW, Cohen NS, Brusilow S and Raijman L. Regulation of urea and citrulline synthesis under physiological conditions. Biochem J 1993; 292 (Pt 1): 241-247.
26. Schimke RT. Repression of enzymes of arginine biosynthesis in mammalian tissue culture. Biochim Biophys Acta 1962; 62: 599-601.
27. Schimke RT. Enzymes of Arginine Metabolism in Mammalian Cell Culture. I. Repression of Argininosuccinate Synthetase and Argininosuccinase. J Biol Chem 1964; 239: 136-145.
28. Guei TR, Liu MC, Yang CP and Su TS. Identification of a liver-specific cAMP response element in the human argininosuccinate synthetase gene. Biochem Biophys Res Commun 2008; 377: 257-261.
29. Husson A, Brasse-Lagnel C, Fairand A, Renouf S and Lavoinne A. Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem 2003; 270: 1887-1899.
30. Furchgott RF and Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373-376.
31. Toda N and Nakanishi-Toda M. Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res 2007; 26: 205-238.
32. Goodwin BL, Solomonson LP and Eichler DC. Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. J Biol Chem 2004; 279: 18353-18360.
33. Wu G and Morris SM, Jr. Arginine metabolism: nitric oxide and beyond. Biochem J 1998; 336 (Pt 1): 1-17.
34. McCormick SM, Eskin SG, McIntire LV, Teng CL, Lu CM, Russell CG and Chittur KK. DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells. Proc Natl Acad Sci USA 2001; 98: 8955-8960.
35. Hecker M, Sessa WC, Harris HJ, Anggard EE and Vane JR. The metabolism of L-arginine and its significance for the biosynthesis of endothelium- derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine. Proc Natl Acad Sci USA 1990; 87: 8612-8616.
36. Shuttleworth CW, Burns AJ, Ward SM, O'Brien WE and Sanders KM. Recycling of L-citrulline to sustain nitric oxide-dependent enteric neurotransmission. Neuroscience 1995; 68: 1295-1304.
37. Su Y and Block ER. Hypoxia inhibits L-arginine synthesis from L-citrulline in porcine pulmonary artery endothelial cells. Am J Physiol 1995; 269: L581-587.
38. Arnt-Ramos LR, O'Brien WE and Vincent SR. Immunohistochemical localization of argininosuccinate synthetase in the rat brain in relation to nitric oxide synthase-containing neurons. Neuroscience 1992; 51: 773-789.
39. Daniel EE, Wang YF, Salapatek AM, Mao YK and Mori M. Arginosuccinate synthetase, arginosuccinate lyase and NOS in canine gastrointestinal tract: immunocytochemical studies. Neurogastroenterology & Motility 2000; 12: 317-334.
40. Shuttleworth CW, Conlon SB and Sanders KM. Regulation of citrulline recycling in nitric oxidedependent neurotransmission in the murine proximal colon. Br J Pharmacol 1997; 120: 707-713.
41. Ellis JL and Conanan N. L-citrulline reverses the inhibition of nonadrenergic, noncholinergic relaxations produced by nitric oxide synthase inhibitors in guinea pig trachea and human bronchus. J Pharmacol Exp Ther 1994; 269: 1073-1078.
42. Van Geldre LA, Timmermans JP and Lefebvre RA. L-citrulline recycling by argininosuccinate synthetase and lyase in rat gastric fundus. European Journal of Pharmacology 2002; 455: 149-160.
43. Swamy M, Salleh MJ, Sirajudeen KN, Yusof WR and Chandran G. Nitric oxide (no), citrulline - no cycle enzymes, glutamine synthetase and oxidative stress in anoxia (hypobaric hypoxia) and reperfusion in rat brain. Int J Med Sci 2010; 7: 147-154.
44. Xie L and Gross SS. Argininosuccinate synthetase overexpression in vascular smooth muscle cells potentiates immunostimulantinduced NO production. J Biol Chem 1997; 272: 16624-16630.
45. Xie L, Hattori Y, Tume N and Gross SS. The preferred source of arginine for high-output nitric oxide synthesis in blood vessels. Semin Perinatol 2000; 24: 42-45.
46. Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA and Michel T. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem 1996; 271: 22810-22814.
47. Tagawa A, Mezzacasa A, Hayer A, Longatti A, Pelkmans L and Helenius A. Assembly and trafficking of caveolar domains in the cell: caveolae as stable, cargo-triggered, vesicular transporters. J Cell Biol 2005; 170: 769-779.
48. Fulton D, Fontana J, Sowa G, Gratton JP, Lin M, Li KX, Michell B, Kemp BE, Rodman D and Sessa WC. Localization of endothelial nitricoxide synthase phosphorylated on serine 1179 and nitric oxide in Golgi and plasma membrane defines the existence of two pools of active enzyme. J Biol Chem 2002; 277: 4277-4284.
49. Sessa WC, Garcia-Cardena G, Liu J, Keh A, Pollock JS, Bradley J, Thiru S, Braverman IM, Desai KM. The Golgi association of endothelial nitric oxide synthase is necessary for the efficient synthesis of nitric oxide. J Biol Chem 1995; 270 (30):17641-17644.
50. Schilling K, Opitz N, Wiesenthal A, Oess S, Tikkanen R, Muller-Esterl W and Icking A. Translocation of endothelial nitric-oxide synthase involves a ternary complex with caveolin-1 and NOSTRIN. Mol Biol Cell 2006; 17: 3870-3880.
51. Schleicher M, Brundin F, Gross S, Muller-Esterl W and Oess S. Cell cycle-regulated inactivation of endothelial NO synthase through NOSIPdependent targeting to the cytoskeleton. Mol Cell Biol 2005; 25: 8251-8258.
52. Zimmermann K, Opitz N, Dedio J, Renne C, Muller-Esterl W and Oess S. NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 2002; 99: 17167-17172.
53. Icking A, Matt S, Opitz N, Wiesenthal A, Muller-Esterl W and Schilling K. NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS. J Cell Sci 2005; 118: 5059-5069.
54. Rogers QR, Freedland RA and Symmons RA. In vivo synthesis and utilization of arginine in the rat. Am J Physiol 1972; 223: 236-240.
55. Davis TA, Nguyen HV, Garcia-Bravo R, Fiorotto ML, Jackson EM, Lewis DS, Lee DR and Reeds PJ. Amino acid composition of human milk is not unique. J Nutr 1994; 124: 1126-1132.
56. Windmueller HG and Spaeth AE. Source and fate of circulating citrulline. Am J Physiol 1981; 241: E473-480.
57. Brosnan ME and Brosnan JT. Renal arginine metabolism. J Nutr 2004; 134: 2791S-2795S; discussion 2796S-2797S.
58. Levillain O, Hus-Citharel A, Morel F and Bankir L. Localization of arginine synthesis along rat nephron. Am J Physiol 1990; 259: F916-923.
59. Walker JB. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 1979; 50: 177-242.
60. Nasrallah F, Feki M and Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatr Neurol 2010; 42: 163-171.
61. Flam BR, Eichler DC and Solomonson LP. Endothelial nitric oxide production is tightly coupled to the citrulline-nitric oxide cycle. Nitric Oxide 2007; 17: 115-121.
62. Shen LJ, Beloussow K and Shen WC. Modulation of arginine metabolic pathways as the potential anti-tumor mechanism of recombinant arginine deiminase. Cancer Lett 2006; 231: 30-35.
63. Topal G, Brunet A, Walch L, Boucher JL and David-Dufilho M. Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells. J Pharmacol Exp Ther 2006; 318: 1368-1374.
64. Delage B, Fennell DA, Nicholson L, McNeish I, Lemoine NR, Crook T and Szlosarek PW. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer 2010; 126: 2762-2772.
65. Ensor CM, Holtsberg FW, Bomalaski JS and Clark MA. Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Cancer Res 2002; 62: 5443-5450.
66. Bach SJ and Swaine D. The Effect of Arginase on the Retardation of Tumour Growth. Br J Cancer 1965; 19: 379-386.
67. Yeatman TJ, Risley GL and Brunson ME. Depletion of dietary arginine inhibits growth of metastatic tumor. Arch Surg 1991; 126: 1376-1381; discussion 1381-1372.
68. Scott L, Lamb J, Smith S and Wheatley DN. Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells. Br J Cancer 2000; 83: 800-810.
69. Philip R, Campbell E and Wheatley DN. Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures. Br J Cancer 2003; 88: 613-623.
70. Wheatley DN. Controlling cancer by restricting arginine availability--arginine-catabolizing enzymes as anticancer agents. Anticancer Drugs 2004; 15: 825-833.
71. Miyazaki K, Takaku H, Umeda M, Fujita T, Huang WD, Kimura T, Yamashita J and Horio T. Potent growth inhibition of human tumor cells in culture by arginine deiminase purified from a culture medium of a Mycoplasma-infected cell line. Cancer Res 1990; 50: 4522-4527.
72. Takaku H, Matsumoto M, Misawa S and Miyazaki K. Anti-tumor activity of arginine deiminase from Mycoplasma argini and its growthinhibitory mechanism. Jpn J Cancer Res 1995; 86: 840-846.
73. Takaku H, Takase M, Abe S, Hayashi H and Miyazaki K. In vivo anti-tumor activity of arginine deiminase purified from Mycoplasma arginini. Int J Cancer 1992; 51: 244-249.
74. Izzo F, Marra P, Beneduce G, Castello G, Vallone P, De Rosa V, Cremona F, Ensor CM, Holtsberg FW, Bomalaski JS, Clark MA, Ng C and Curley SA. Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies. J Clin Oncol 2004; 22: 1815-1822.
75. Ascierto PA, Scala S, Castello G, Daponte A, Simeone E, Ottaiano A, Beneduce G, De Rosa V, Izzo F, Melucci MT, Ensor CM, Prestayko AW, Holtsberg FW, Bomalaski JS, Clark MA, Savaraj N, Feun LG and Logan TF. Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies. J Clin Oncol 2005; 23: 7660-7668.
76. Kobayashi E, Masuda M, Nakayama R, Ichikawa H, Satow R, Shitashige M, Honda K, Yamaguchi U, Shoji A, Tochigi N, Morioka H, Toyama Y, Hirohashi S, Kawai A and Yamada T. Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma. Mol Cancer Ther 2010; 9: 535-544.
77. Szlosarek PW, Grimshaw MJ, Wilbanks GD, Hagemann T, Wilson JL, Burke F, Stamp G and Balkwill FR. Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer. Int J Cancer 2007; 121: 6-11.
78. Kobayashi K, Jackson MJ, Tick DB, O'Brien WE and Beaudet AL. Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia. J Biol Chem 1990; 265: 11361-11367.
79. Jinno Y, Matuo S, Nomiyama H, Shimada K and Matsuda I. Novel structure of the 5' end region of the human argininosuccinate synthetase gene. J Biochem (Tokyo) 1985; 98: 1395-1403.
80. Jinno Y, Nomiyama H, Matuo S, Shimada K, Matsuda I and Saheki T. Structure of the 5' end region of the human argininosuccinate synthetase gene. J Inherit Metab Dis 1985; 8: 157-159.
81. Anderson GM and Freytag SO. Synergistic activation of a human promoter in vivo by transcription factor Sp1. Mol Cell Biol 1991; 11: 1935-1943.
82. Chin AC and Fournier RE. A genetic analysis of extinction: trans-regulation of 16 liver-specific genes in hepatoma-fibroblast hybrid cells. Proc Natl Acad Sci U S A 1987; 84: 1614-1618.
83. Ruppert S, Boshart M, Bosch FX, Schmid W, Fournier RE and Schutz G. Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes. Cell 1990; 61: 895-904.
84. Morris SM, Jr., Moncman CL, Rand KD, Dizikes GJ, Cederbaum SD and O'Brien WE. Regulation of mRNA levels for five urea cycle enzymes in rat liver by diet, cyclic AMP, and glucocorticoids. Arch Biochem Biophys 1987; 256: 343-353.
85. Boshart M, Weih F, Nichols M and Schutz G. The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMPdependent protein kinase. Cell 1991; 66: 849-859.
86. Tsai WB, Aiba I, Lee SY, Feun L, Savaraj N and Kuo MT. Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1alpha/Sp4. Mol Cancer Ther 2009; 8: 3223-3233.
87. Anderson HD, Rahmutula D and Gardner DG. Tumor necrosis factor-alpha inhibits endothelial nitric-oxide synthase gene promoter activity in bovine aortic endothelial cells. J Biol Chem 2004; 279: 963-969.
88. Lai PF, Mohamed F, Monge JC and Stewart DJ. Downregulation of eNOS mRNA expression by TNFalpha: identification and functional characterization of RNA-protein interactions in the 3'UTR. Cardiovasc Res 2003; 59: 160-168.
89. Barsacchi R, Perrotta C, Bulotta S, Moncada S, Borgese N and Clementi E. Activation of endothelial nitric-oxide synthase by tumor necrosis factor-alpha: a novel pathway involving sequential activation of neutral sphingomyelinase, phosphatidylinositol-3' kinase, and Akt. Mol Pharmacol 2003; 63: 886-895.
90. Takahashi S and Mendelsohn ME. Synergistic activation of endothelial nitric-oxide synthase (eNOS) by HSP90 and Akt: calciumindependent eNOS activation involves formation of an HSP90-Akt-CaM-bound eNOS complex. J Biol Chem 2003; 278: 30821-30827.
91. Kwon H and Pak Y. Prolonged tyrosine kinase activation of insulin receptor by pY27-caveolin-2. Biochem Biophys Res Commun 2009;
92. Goodwin B, Pendleton L, Levy M, Solomonson L and Eichler D. Tumor Necrosis Factor-{alpha} Reduces Substrate Availability for Nitric Oxide Production via Down-Regulation of Argininosuccinate Synthase. Am J Physiol Heart Circ Physiol 2007; 293: H1115-1121.
93. Rothwarf DM and Karin M. The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE1999; 1999: RE1.
94. Goodwin BL, Corbin KD, Pendleton LC, Levy MM, Solomonson LP and Eichler DC. Troglitazone up-regulates vascular endothelial argininosuccinate synthase. Biochem Biophys Res Commun 2008; 370: 254-258.
95. Polikandriotis JA, Mazzella LJ, Rupnow HL and Hart CM. Peroxisome proliferator-activated receptor gamma ligands stimulate endothelial nitric oxide production through distinct peroxisome proliferator-activated receptor gammadependent mechanisms. Arterioscler Thromb Vasc Biol 2005; 25: 1810-1816.
96. Cho DH, Choi YJ, Jo SA and Jo I. Nitric oxide production and regulation of endothelial nitricoxide synthase phosphorylation by prolonged treatment with troglitazone: evidence for involvement of peroxisome proliferator-activated receptor (PPAR) gamma-dependent and PPARgamma-independent signaling pathways. J Biol Chem 2004; 279: 2499-2506.
97. Fra AM, Williamson E, Simons K and Parton RG. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc Natl Acad Sci U S A 1995; 92: 8655-8659.
98. Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H and Kurzchalia TV. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 2001; 293: 2449-2452.
99. Ju H, Zou R, Venema VJ and Venema RC. Direct interaction of endothelial nitric-oxide synthase and caveolin-1 inhibits synthase activity. J Biol Chem 1997; 272: 18522-18525.
100. Ghosh S, Gachhui R, Crooks C, Wu C, Lisanti MP and Stuehr DJ. Interaction between caveolin-1 and the reductase domain of endothelial nitric-oxide synthase. Consequences for catalysis. J Biol Chem 1998; 273: 22267-22271.
101. Meijer HA and Thomas AA. Control of eukaryotic protein synthesis by upstream open reading frames in the 5'-untranslated region of an mRNA. Biochem J 2002; 367: 1-11.
102. Pendleton LC, Goodwin BL, Flam BR, Solomonson LP and Eichler DC. Endothelial argininosuccinate synthase mRNA 5 ́-untranslated region diversity. Infrastructure for tissue-specific expression. J Biol Chem 2002; 277: 25363-25369.
103. Pendleton LC, Goodwin BL, Solomonson LP and Eichler DC. Regulation of endothelial argininosuccinate synthase expression and NO production by an upstream open reading frame. J Biol Chem 2005; 280: 24252-24260.
104. Zhao Y, Zhang J, Li H, Li Y, Ren J, Luo M and Zheng X. An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability. J Biol Chem 2008; 283: 11004-11013.
105. Hao G, Xie L and Gross SS. Argininosuccinate Synthetase is Reversibly Inactivated by SNitrosylation in Vitro and in Vivo. Journal of Biological Chemistry 2004; 279: 36192-36200.
106. Imami K, Sugiyama N, Kyono Y, Tomita M and Ishihama Y. Automated phosphoproteome analysis for cultured cancer cells by twodimensional nanoLC-MS using a calcined titania/ C18 biphasic column. Anal Sci 2008; 24: 161-166.
107. Corbin KD, Pendleton LC, Solomonson LP and Eichler DC. Phosphorylation of argininosuccinate synthase by protein kinase A. Biochem Biophys Res Commun 2008; 377: 1042-1046.