Skip to main content
SpringerLink
Log in

l-Arginine Uptake by Cells

  • Chapter
  • First Online:
Book cover L-Arginine in Clinical Nutrition

Part of the book series: Nutrition and Health ((NH))

Abstract

Cardiovascular disease accounted for nearly 40 % of all deaths in the USA in 2000 (American Heart Association, Heart Disease and Stroke Statistics—2003 Update. American Heart Association, 2002). Hypertension, heart failure, and metabolic diseases such as obesity, type 2 diabetes mellitus, and hypercholesterolaemia have impaired endothelial function as a common feature (Bode-Böger et al., Pharmacol Therapeut 114:295–306, 2007). Endothelial dysfunction, arising from underlying reduced bioavailability of nitric oxide (NO), causes inflammation and oxidative stress to drive the atherosclerotic process (Tousoulis et al., Curr Vasc Pharmacol 10:4–18, 2012; Vita, Circulation 124:e906–e912, 2011).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. American Heart Association. Heart disease and stroke statistics—2003 update. Dallas, TX: American Heart Association; 2002.

    Google Scholar 

  2. Bode-Böger SM, Scalera F, Ignarro LJ. The l-arginine paradox: importance of the l-arginine/asymmetrical dimethylarginine ratio. Pharmacol Ther. 2007;114:295–306.

    Google Scholar 

  3. Tousoulis D, Kampoli A-M, Papageorgiou CTN, Stefanadis C. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 2012;10:4–18.

    Article  CAS  PubMed  Google Scholar 

  4. Vita JA. Endothelial function. Circulation. 2011;124:e906–12.

    Article  PubMed  Google Scholar 

  5. Qain J, Fulton D. Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium. Front Physiol. 2013;4:1–11.

    Google Scholar 

  6. Sessa WC, Hecker M, Mitchell JA, Vane JR. The metabolism of l-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of l-arginine by cultured endothelial cells. Proc Natl Acad Sci USA. 1990;87:8607–11.

    Google Scholar 

  7. Simmons WW, Closs EI, Cunningham JM, et al. Cytokines and insulin induce cationic amino acid transporter (CAT) expression in cardiac myocytes. J Biol Chem. 1996;271:11694–702.

    Article  CAS  PubMed  Google Scholar 

  8. Chin-Dusting JPF, Willems L, Kaye DM. l-arginine transporters in cardiovascular disease: a novel therapeutic target. Pharmacol Ther. 2007;116:428–36.

    Google Scholar 

  9. Siani A, Pagano E, Lacone R, et al. Blood pressure and metabolic changes during l-arginine supplementation in humans. Am J Hypertens. 2000;13:547–51.

    Google Scholar 

  10. Ast J, Jablecka A, Bogdanski P, et al. Evaluation of the antihypertensive effect of l-arginine. Med Sci Monit. 2010;16:CR266–71.

    Google Scholar 

  11. Dioguardi FS. To give or not to give? Lessons from the l-arginine paradox. J Nutrigenet Nutrigenomics. 2011;4:90–8.

    Google Scholar 

  12. Penttinen J, Pennanen S, Liesivuori J. Indicators of l-arginine metabolism and cardiovascular risk factors. A cross-sectional study in healthy middle-aged men. Amino Acids. 2000;18:199–206.

    Google Scholar 

  13. Moss MB, Brunini TMC, Soares de Moura R. Diminished l-arginine bioavailability in hypertension. Clin Sci. 2004;107:391–7.

    Google Scholar 

  14. Perticone F, Sciacqua A, Maio R, et al. Asymmetric dimethylarginine, l-arginine and endothelial dysfunction in essential hypertension. J Am Coll Cardiol. 2005;46:518–23.

    Google Scholar 

  15. Naidoo C, Cromarty AD, Snyman T, et al. Relationships between plasma amino acid concentrations and blood pressure in South Africans of African descent. SA Heart. 2009;6:142–7.

    Google Scholar 

  16. Mendes-Ribeiro AC, Brunini TMC, Ellory JC, Mann GE. Abnormalities in l-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure. Cardiovasc Res. 2001;49:697–712.

    Google Scholar 

  17. Devés R, Boyd CAR. Transporters for cationic amino acids in animal cells: discovery, structure, and function. Physiol Rev. 1998;78:487–545.

    PubMed  Google Scholar 

  18. Mann GE, Yudilevich DL, Sobrevia L. Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev. 2003;83:183–252.

    Article  CAS  PubMed  Google Scholar 

  19. Bröer S. Amino acid transport across mammalian intestinal and renal epithelia. Physiol Rev. 2008;88:249–86.

    Article  PubMed  Google Scholar 

  20. Closs EI, Boissel JP, Habermeier A, Rotmann A. Structure and function of cationic amino acid transporters (CATs). J Membr Biol. 2006;213(2):67–77.

    Article  CAS  PubMed  Google Scholar 

  21. Díaz-Pérez F, Radojkovic C, Aguilera V, et al. l-Arginine transport and nitric oxide synthesis in human endothelial progenitor cells. J Cardiovasc Pharmacol. 2012;60:439–49.

    Google Scholar 

  22. Devés R, Chavez P, Boyd CAR. Identification of a new transport system (y+L) in human erythrocytes that recognizes lysine and leucine with high affinity. J Physiol. 1992;454:491–501.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Arancibia-Garavilla Y, Toledo F, Casanello P, Sobrevia L. Nitric oxide synthesis requires activity of the cationic and neutral amino acid transport system y+L in human umbilical vein endothelium. Exp Physiol. 2003;88(6):699–710.

    Article  CAS  PubMed  Google Scholar 

  24. White MF, Christensen HN. The two-way flux of cationic amino acids across the plasma membrane of mammalian cells is largely explained by a single transport system. J Biol Chem. 1982;257:10069–80.

    CAS  PubMed  Google Scholar 

  25. Durante W, Liao L, Iftikhar I, et al. Differential regulation of l-arginine transport and nitric oxide production by vascular smooth muscle and endothelium. Circ Res. 1996;78:1075–82.

    Google Scholar 

  26. Patel JM, Abeles AJ, Block ER. Nitric oxide exposure and sulfhydryl modulation alter l-arginine transport in cultured pulmonary artery endothelial cells. Free Radic Biol Med. 1996;20:629–37.

    Google Scholar 

  27. Sala R, Rotoli BM, Colla E, et al. Two-way arginine transport in human endothelial cells: TNF-α stimulation is restricted to system y+. Am J Physiol Cell Physiol. 2002;282:C134–43.

    CAS  PubMed  Google Scholar 

  28. Closs EI, Gräf P, Habermeier A, et al. Human cationic amino acid transporters hCAT-1, hCAT-2A, and hCAT-2B: three related carriers with distinct transport properties. Biochemistry. 1997;36:6462–8.

    Article  CAS  PubMed  Google Scholar 

  29. Speake PF, Glazier JD, Ayuk PT-Y, et al. l-Arginine transport across the basal plasma membrane of the syncytiotrophoblast of the human placenta from normal and pre-eclamptic pregnancies. J Clin Endocrinol Metab. 2003;88:4287–92.

    Google Scholar 

  30. Parnell MM, Chin-Dusting JPF, Starr J, Kaye DM. In vivo and in vitro evidence of Ach-stimulated l-arginine uptake. Am J Physiol Heart Circ Physiol. 2004;287:H3965–4000.

    Google Scholar 

  31. Nel MJ, Woodiwiss AJ, Candy GP. Modeling of cellular l-arginine uptake by more than one transporter. J Membr Biol. 2012;245:1–13.

    Google Scholar 

  32. Malo C, Berteloot A. Analysis of kinetic data in transport studies: new insights from kinetic studies of Na+-D-glucose co-transport in human intestinal brush-border membrane vesicles using a fast sampling, rapid filtration apparatus. J Membr Biol. 1991;122:127–41.

    Article  CAS  PubMed  Google Scholar 

  33. Devés R, Angelo S, Chávez P. N-Ethylmaleimide discriminates between two lysine transport systems in human erythrocytes. J Physiol. 1993;468:753–66.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Angelo S, Irarrázabal C, Devés R. The binding specificity of amino acid transport system y+L in human erythrocytes is altered by monovalent cations. J Membr Biol. 1996;153:37–44.

    Article  CAS  PubMed  Google Scholar 

  35. Dall’Asta V, Bussolati O, Sala R, et al. Arginine transport through system y+L in cultured human fibroblasts: normal phenotype of cells from LPI subjects. Am J Physiol Cell Physiol. 2000;279:C1829–37.

    PubMed  Google Scholar 

  36. Hardy TA, May JM. Coordinate regulation of l-arginine uptake and nitric oxide synthase activity in cultured endothelial cells. Free Radic Biol Med. 2002;32:122–31.

    Google Scholar 

  37. Rotoli BM, Bussolati O, Sala R, et al. The transport of cationic amino acids in human airway cells: expression of system y+L activity and transepithelial delivery of NOS inhibitors. FASEB J. 2005;19(7):810–2.

    CAS  PubMed  Google Scholar 

  38. Cheng Y-C, Prusoff WH. Relationship between the inhibitor constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (I 50 ) of an enzymatic reaction. Biochem Pharmacol. 1973;22:3099–108.

    Article  CAS  PubMed  Google Scholar 

  39. Spears G, Sneyd JGT, Loten EG. A method for deriving kinetic constants for two enzymes acting on the same substrate. Biochem J. 1971;125:1149–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Leatherbarrow RJ. Using linear and non-linear regression to fit biochemical data. Trends Biochem Sci. 1990;15:455–8.

    Article  PubMed  Google Scholar 

  41. Coons DM, Boulton RB, Bisson LF. Computer-assisted nonlinear regression analysis of the multicomponent glucose uptake kinetics of Saccharomyces cerevisae. J Bacteriol. 1995;177:3251–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Walsh R, Martin E, Darvesh S. A versatile equation to describe reversible enzyme inhibition and activation kinetics: modeling β-galactosidase and butyrylcholinesterase. Biochim Biophys Acta. 2007;1770:733–46.

    Article  CAS  PubMed  Google Scholar 

  43. Berteloot A, Malo C, Breton S, Brunette M. Fast sampling, rapid filtration apparatus: principal characteristics and validation from studies of D-glucose transport in human jejuna brush-border membrane vesicles. J Membr Biol. 1991;122:111–25.

    Article  CAS  PubMed  Google Scholar 

  44. Signorello MG, Pascale R, Leoncini G. Transport of l-arginine and nitric oxide formation in human platelets. Eur J Biochem. 2003;270:2005–12.

    Google Scholar 

  45. Christensen HN, Antonioli JA. Cationic amino acid transport in the rabbit reticulocyte. J Biol Chem. 1969;244:1497–504.

    CAS  PubMed  Google Scholar 

  46. Mendes-Ribeiro AC, Brunini TMC, Yaqoob M, et al. Identification of system y+L as the high-affinity transporter for l-Arginine in human platelets: up-regulation of l-Arginine influx in uraemia. Pflügers Arch. 1999;438:573–5.

    Google Scholar 

  47. Rotmann A, Simon A, Martiné U, et al. Activation of classical protein kinase C decreases transport via systems y+ and y+L. Am J Physiol Cell Physiol. 2007;292:C2259–68.

    Article  CAS  PubMed  Google Scholar 

  48. White MF, Gazzola GC, Christensen HN. Cationic amino acid transport into cultured animal cells. I. Influx into cultured human fibroblasts. J Biol Chem. 1982;257:4443–9.

    CAS  PubMed  Google Scholar 

  49. Rajapakse N, Mattson DL. Role of l-arginine in nitric oxide production in health and hypertension. Clin Exp Pharmacol Physiol. 2009;36:249–55.

    Google Scholar 

Download references

Acknowledgements and Conflicts of Interest

The authors gratefully acknowledge the assistance of Ms. F. Scholtz for editing and revision of the manuscript.

The authors referred to and used GraphPadPrism® (Version 5, GraphPad Software Inc., La Jolla, California, USA) in their studies and found the software useful. However, reference to this product is not an endorsement of the software and the authors have no financial conflict of interest by referring to this product. Other software could be used to undertake the required calculations and obtain the results presented.

Author information

Authors and Affiliations

  1. Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, Gauteng, 2193, South Africa

    Geoffrey P. Candy PhD & Marietha J. Nel PhD

Authors
  1. Geoffrey P. Candy PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marietha J. Nel PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Geoffrey P. Candy PhD .

Editor information

Editors and Affiliations

  1. Faculty of Science & Technology Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Department Nutrition and Dietetics Nutritional Sciences Division School of Biomedical & Health Sciences, King’s College London, London, United Kingdom

    Victor R. Preedy

  3. Nutritional Sciences Research Division Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Rajkumar Rajendram

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Candy, G.P., Nel, M.J. (2017). l-Arginine Uptake by Cells. In: Patel, V., Preedy, V., Rajendram, R. (eds) L-Arginine in Clinical Nutrition. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-26009-9_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26009-9_1

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-26007-5

  • Online ISBN: 978-3-319-26009-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation