The fluctuation of free amino acids in serum during acute ischemic stroke

Open access


Currently, little data exists regarding the involvement of free amino acids (AA) in the pathogenesis of ischemic stroke (IS). Thus, our objective was to study the degree of the degree of fluctuation of free amino acids level in serum during the acute phase of IS. The study consisted of eighteen patients (female/male: 10/8; age: 73.1 ± 4.1) with acute IS that was confirmed by way of computed tomography, while twelve sex and age matched individuals were assigned as control group. During the study period, the patients did not receive any supplemental amino acids therapy that could affect the obtained results. The venous blood was obtained after >3 hours fasting at two time-points; time-point 1 – at admission to the hospital; time-point 2 – on day 5 from stroke onset. The blood for control purposes was collected only once, and the blood collection at time-point 1 was done before thrombolytic treatment (nine patients). The amino acids were identified using the Amino Acids Analyser (AAA 400) by INGOS Corp., Praha, Czech Republic. Our results revealed a statistically significant increase of glutamate, cystine and methionine on day 1 of stroke, in comparison to control, whereas, proline level was decreased on day 1 of stroke – in comparison to control serum. On comparing day 5 to the initial day of IS, elevation was observed of levels of asparagine, glycine, tyrosine, arginine, threonine, valine, leucine and phenylalanine. It can be said, then, that ischemic stroke induces both essential and nonessential amino acid fluctuations. Moreover, the decrease in proline and glutamine serum level with the simultaneous increase in the concentration of branch chain amino acids, Glu and Thr suggests a violent mobilization of the body’s proteins. Thus, a decrease of Pro and a simultaneous increase of Glu serum level could be considered as a marker of acute IS.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Brasse-Lagnel C. et al.: Glutamine stimulates argininosuccinate synthetase gene expression through cytosolic O-glycosylation of Sp1 in Caco-2 cells. J Biol Chem. 278 52504 2003.

  • 2. Castillo J. Rodriguez I.: Biochemical changes and inflammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice. Cerebrovasc Dis. 17 Suppl 1 7 2004.

  • 3. Harston George W J et al.: The contribution of L-arginine to the neurotoxicity of recombinant tissue plasminogen activator following cerebral ischemia: a review of rtPA neurotoxicity. J Cereb Blood Flow Metab. 30 1804 2010.

  • 4. Horecka A. et al.: Actylise treatment does not influence nitric oxide metabolites serum level. Pharmacol Rep 2016.

  • 5. Huang Y.F. Wang Y. Watford M.: Glutamine directly downregulates glutamine synthetase protein levels in mouse C2C12 skeletal muscle myotubes. J Nutr. 137 1357 2007.

  • 6. Karna E. Szoka L. Palka J.A.: Captopril-dependent inhibition of collagen biosynthesis in cultured fibroblasts. Pharmazie. 65 614 2010.

  • 7. Kimberly W.T. et al.: Metabolite profiling identifies a branched chain amino acid signature in acute cardioembolic stroke. Stroke. 44 1389 2013.

  • 8. Kuklina E.V. et al.: Epidemiology and prevention of stroke: a worldwide perspective. Expert Rev Neurother. 12 199 2012.

  • 9. Kurzepa J. et al.: Thrombolytic treatment decreases glutamate/GABA ratio in serum during acute ischaemic stroke: a pilot study. Neurol Res. 37 934 2015.

  • 10. Miao Y. Liao J.K.: Potential serum biomarkers in the pathophysiological processes of stroke. Expert Rev Neurother. 14 173 2014.

  • 11. Nagata C. et al.: Dietary intakes of glutamic Acid and glycine are associated with stroke mortality in Japanese adults. J Nutr. 145 720 2015.

  • 12. Newsholme P. et al.: New insights into amino acid metabolism beta-cell function and diabetes. Clin Sci (Lond). 108 185 2005.

  • 13. Phang J.M. et al.: Proline metabolism and cancer: emerging links to glutamine and collagen. Curr Opin Clin Nutr Metab Care. 18 71 2015.

  • 14. Raman K. Pare G.: Of stroke and biomarkers: the elusive quest for a clinical biomarker panel. Clin Biochem. 46 705 2013.

  • 15. Salemi G. et al.: Blood levels of homocysteine cysteine glutathione folic acid and vitamin B12 in the acute phase of atherothrombotic stroke. Neurol Sci. 30 361 2009.

  • 16. Skovierova H. et al.: Effect of homocysteine on survival of human glial cells. Physiol Res 2015.

  • 17. Staszewski J. et al.: Intravenous insulin therapy in the maintenance of strict glycemic control in nondiabetic acute stroke patients with mild hyperglycemia. J Stroke Cerebrovasc Dis. 20 150 2011.

  • 18. Szpetnar M. Pasternak K. Boguszewska A.: Branched chain amino acids (BCAAs) in heart diseases (ischaemic heart disease and myocardial infarction). Ann Univ Mariae Curie Sklodowska Med. 59 91 2004.

  • 19. Takemoto Y.: Intracisternally injected L-proline activates hypothalamic supraoptic but not paraventricular vasopressin-expressing neurons in conscious rats. J Amino Acids. 2011 230613 2011.

  • 20. Tom A. Nair K.S.: Assessment of branched-chain amino Acid status and potential for biomarkers. J Nutr. 136 324S-30S 2006.

  • 21. Watford M.: Lowered concentrations of branched-chain amino acids result in impaired growth and neurological problems: insights from a branched-chain alpha-keto acid dehydrogenase complex kinase-deficient mouse model. Nutr Rev. 65 167 2007.

  • 22. Wong Peter T H et al.: High plasma cyst(e)ine level may indicate poor clinical outcome in patients with acute stroke: possible involvement of hydrogen sulfide. J Neuropathol Exp Neurol. 65 109 2006.

  • 23. Wu G.: Amino acids: metabolism functions and nutrition. Amino Acids. 37 1 2009.

  • 24. Wu G. et al.: Arginine metabolism and nutrition in growth health and disease. Amino Acids. 37 153 2009.

Journal information
Impact Factor

CiteScore 2018: 0.32

SCImago Journal Rank (SJR) 2018: 0.154
Source Normalized Impact per Paper (SNIP) 2018: 0.285

Cited By
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 260 152 7
PDF Downloads 121 74 4