DOI: https://doi.org/10.24959/nphj.20.19

Amino acids in cardiology, gastroenterology and neurology

N. A. Gorchakova, A. V. Zaychenko, K. Yu. Sorokopud

Abstract


Aim. To determine the role of amino acids in cardiology, gastroenterology and neurology.

Materials and methods. The material of the article was the literature data on the use of amino acids in cardiology, gastroenterology and neurology, which were processed by methods of generalization and systematization.

Results and discussion. Data on the role of leucine, isoleucine, and valine in the pathogenesis of heart failure and the effect on their metabolism for prophylactic and therapeutic purposes are provided. The antiatherogenic role of glycine and leucine, taurine and arginine in the metabolic syndrome has been highlighted. The neuroprotective and cardioprotective values of L-arginine, and the neurotransmitter value of glutamate have been indicated. The attention is focused on the role of amino acids in the implementation of hepatoprotection.

Conclusions. In the pathogenesis of cardiovascular, gastroenterological, neurological diseases a significant role is given to amino acids. The analysis of the literature data confirms the rationality of the introduction of drugs containing branched-chain amino acids in order to achieve cardioprotective, neuroprotective and hepatoprotective effects.

Keywords


amino acids; pathogenesis; cardiology; gastroenterology; neurology

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References


Huang, Y., Zhou, M., Sun, H., & Wang, Y. (2011). Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit? Cardiovascular Research, 90 (2), 220–223. https://doi.org/10.1093/cvr/cvr070

D’Antona, G., Ragni, M., Cardile, A., Tedesco, L., Dossena, M., Bruttini, F., … Nisoli, E. (2010). Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice. Cell Metabolism, 12 (4), 362–372. https://doi.org/10.1016/j.cmet.2010.08.016

Michas, G., Micha, R., & Zampelas, A. (2014). Dietary fats and cardiovascular disease: Putting together the pieces of a complicated puzzle. Atherosclerosis, 234 (2), 320–328. https://doi.org/10.1016/j.atherosclerosis.2014.03.013

Rom, O., Grajeda-Iglesias, C., Najjar, M., Abu-Saleh, N., Volkova, N., Dar, D. E., … Aviram, M. (2017). Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice: a key role for triglyceride metabolism. The Journal of Nutritional Biochemistry, 45, 24–38. https://doi.org/10.1016/j.jnutbio.2017.02.023

Oren, R., Aviram, M. (2017). It is not just lipids: proatherogenic vs. antiatherogenic roles for amino acids in macrophage foam cell formation. Current Opinion in Lipidology, 28 (1), 85–87.

Zhao, Y., Dai, X., Zhou, Z., Zhao, G., Wang, X., & Xu, M. (2015). Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice. Acta Pharmacologica Sinica, 37 (2), 196–203. https://doi.org/10.1038/aps.2015.88

Shah, S. H., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Crosslin, D. R., Haynes, C., … Kraus, W. E. (2010). Association of a Peripheral Blood Metabolic Profile With Coronary Artery Disease and Risk of Subsequent Cardiovascular Events. Circulation: Cardiovascular Genetics, 3 (2), 207–214. https://doi.org/10.1161/circgenetics.109.852814

Gannon, N. P., Schnuck, J. K., & Vaughan, R. A. (2018). BCAA Metabolism and Insulin Sensitivity - Dysregulated by Metabolic Status? Molecular Nutrition & Food Research, 62 (6), 1700756. https://doi.org/10.1002/mnfr.201700756

Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Tuulia, Hyotylainen., Trine, Nielsen., Benjamin, A. H. Jensen., Kristoffer, Forslund., … Falk, Hildebrand. (2016). Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 535 (7612), 376–381.

Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., … Svetkey, L. P. (2009). A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance. Cell Metabolism, 9 (4), 311–326. https://doi.org/10.1016/j.cmet.2009.02.002

Bifari, F., & Nisoli, E. (2016). Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view. British Journal of Pharmacology, 174 (11), 1366–1377. https://doi.org/10.1111/bph.13624

Sun, L., Hu, C., Yang, R., Lv, Y., Yuan, H., Liang, Q., … Yang, Z. (2017). Association of circulating branched-chain amino acids with cardiometabolic traits differs between adults and the oldest-old. Oncotarget, 8 (51), 88882–88893. https://doi.org/10.18632/oncotarget.21489

Paramjit, S. T., James, Thliveris., Yan-Jan Xu, Aroutiounova, N., Naranjan, S. Dh.(2011). Effects of amino acid supplementation on myocardial cell damage and cardiac function in diabetes. Exp Clin Cardiol., 16 (3), e17–e22.

Ito, T., Schaffer, S. W., & Azuma, J. (2011). The potential usefulness of taurine on diabetes mellitus and its complications. Amino Acids, 42 (5), 1529–1539. https://doi.org/10.1007/s00726-011-0883-5

Rizzo, A. M., Berselli, P., Zava, S., Montorfano, G., Negroni, M., Corsetto, P., & Berra, B. (2010). Endogenous Antioxidants and Radical Scavengers. Bio-Farms for Nutraceuticals, 52–67. https://doi.org/10.1007/978-1-4419-7347-4_5

Clark, A. T., G. Maddaford, T., S. Tappia, P., E. Heyliger, C., K. Ganguly, P., & N. Pierce, G. (2010). Restoration of Cardiomyocyte Function in Streptozotocin-Induced Diabetic Rats after Treatment with Vanadate in a Tea Decoction. Current Pharmaceutical Biotechnology, 11 (8), 906–910. https://doi.org/10.2174/138920110793261999

Harris, R. Lieberman. (1999). Amino Acid and Protein Requirements: Cognitive Performance, Stress, and Brain Function. Protein and Amino Acids, 289–307.

Nikolic, J., Bjelakovic, G., & Stojanovic, I.(2003). Effect of caffeine on metabolism of L-arginine in the brain. Guanidino Compounds in Biology and Medicine, 125–128. https://doi.org/10.1007/978-1-4615-0247-0_18

Tuncer, M. C., Hatipoglu, E. S., Ozturk, H., Kervancioglu, P., & Buyukbayram, H. (2005). The Effects of L-Arginine on Neurological Function, Histopathology, and Expression of Hypoxia-Inducible Factor-1 Alpha following Spinal Cord Ischemia in Rats. European Surgical Research, 37 (6), 323–329. https://doi.org/10.1159/000090331

Ali-Sisto, T., Tolmunen, T., Viinamäki, H., Mäntyselkä, P., Valkonen-Korhonen, M., Koivumaa-Honkanen, H., … Lehto, S. M. (2018). Global arginine bioavailability ratio is decreased in patients with major depressive disorder. Journal of Affective Disorders, 229, 145–151. https://doi.org/10.1016/j.jad.2017.12.030

Koga, Y., Povalko, N., Inoue, E., Nakamura, H., Ishii, A., Suzuki, Y., … Fujii, K. (2018). Therapeutic regimen of l-arginine for MELAS: 9-year, prospective, multicenter, clinical research. Journal of Neurology, 265 (12), 2861–2874. https://doi.org/10.1007/s00415-018-9057-7

Chia-Ni, Lin., Chin-Chang, Huang., Kuo-Lun, Huang., Kun-Ju, Lin., Tzu-Chen, Yen., Hung-Chou, Kuo. (2019). A metabolomic approach to identifying biomarkers in blood of Alzheimer’s disease. Ann Clin Transl Neurol., 6 (3), 537–545. https://doi.org/10.1002/acn3.726

Mapstone, M., Lin, F., Nalls, A. N., Cheema, A. K., Singleton, A. B., Fiandaca, M. S., Federoff, H. J. (2017). What success can teach us about failure: the plasma metabolome of older adults with superior memory and lessons for Alzheimer’s disease. Neurobiol Aging, 51, 148–155. https://doi.org/10.1016/j.neurobiolaging.2016.11.007

Colton, C. A., Mott, R. T., Sharpe, H., Xu, Q., Van Nostrand, W. E., & Vitek, M. P. (2006). Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. Journal of Neuroinflammation, 3 (1), 27. https://doi.org/10.1186/1742-2094-3-27

Liu, P., Fleete, M. S., Jing, Y., Collie, N. D., Curtis, M. A., Waldvogel, H. J., Faull, R. L. M., Abraham, W. C., Zhang, H. (2014). Altered arginine metabolism in Alzheimer’s disease brains. Neurobiol Aging, 35 (9), 1992–2003. https://doi.org/10.1016/j.neurobiolaging.2014.03.013

Kan, M. J., Lee, J. E., Wilson, J. G., Everhart, A. L., Brown, C. M., Hoofnagle, A. N., … Jansen, M. (2015). Arginine deprivation and immune suppression in a mouse model of Alzheimer’s disease. Journal Neurosci, 35, 5969–5982. https://doi.org/10.1523/jneurosci.4668-14.2015

Sarchielli, P., Greco, L., Floridi, A., Floridi, A., & Gallai, V. (2003). Excitatory Amino Acids and Multiple Sclerosis. Archives of Neurology, 60 (8), 1082–1088. https://doi.org/10.1001/archneur.60.8.1082

Al Gawwam, G., & Sharquie, I.K. (2017). Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis. The Scientific World Journal, 2017, 1–5. https://doi.org/10.1155/2017/9320802

Cicalini, I., Rossi, C., Pieragostino, D., Agnifili, L., Mastropasqua, L., di Ioia, M., … Del Boccio, P. (2019). Integrated Lipidomics and Metabolomics Analysis of Tears in Multiple Sclerosis: An Insight into Diagnostic Potential of Lacrimal Fluid. International Journal of Molecular Sciences, 20 (6), 1265. https://doi.org/10.3390/ijms20061265

Benussi, A., Alberici, A., Buratti, E., Ghidoni, R., Gardoni, F., Di Luca, M., … Borroni, B. (2019). Toward a Glutamate Hypothesis of Frontotemporal Dementia. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.00304

Kawaguchi, T., Taniguchi, E., & Sata, M. (2013). Effects of Oral Branched-Chain Amino Acids on Hepatic Encephalopathy and Outcome in Patients With Liver Cirrhosis. Nutrition in Clinical Practice, 28 (5), 580–588. https://doi.org/10.1177/0884533613496432

Gluud, L. L., Dam, G., Les, I., Marchesini, G., Borre, M., Aagaard, N. K., & Vilstrup, H. (2017). Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd001939.pub4

Kawaguchi, T., Shiraishi, K., Ito, T., Suzuki, K., Koreeda, C., Ohtake, T., … Suzuki, K. (2014). Branched-Chain Amino Acids Prevent Hepatocarcinogenesis and Prolong Survival of Patients With Cirrhosis. Clinical Gastroenterology and Hepatology, 12 (6), 1012–1018.e1. https://doi.org/10.1016/j.cgh.2013.08.050

Hagiwara, A., Nishiyama, M., & Ishizaki, S. (2012). Branched-chain amino acids prevent insulin-induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2-dependent mechanisms. Journal of Cellular Physiology, 227 (5), 2097–2105. https://doi.org/10.1002/jcp.22941

Gaggini, M., Carli, F., Rosso, C., Buzzigoli, E., Marietti, M., Della Latta, V., … Gastaldelli, A. (2017). Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance. Hepatology, 67 (1), 145–158. https://doi.org/10.1002/hep.29465


GOST Style Citations


1. Branched-chain amino acid metabolism in heart disease : an epiphenomenon or a real culprit? / Ying Huang, Meiyi Zhou, Haipeng Sun, Yibin Wang // Cardiovascular Res. – 2011. – Vol. 90, Issue 2. – P. 220–223. https://doi.org/10.1093/cvr/cvr070

 

2. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice / G. D’Antona, M. Ragni et al. // Cell Metab. – 2010. – Vol. 12, Issue 4. – P. 362–372. https://doi.org/10.1016/j.cmet.2010.08.016 

 

3. Michas, G. Dietary fats and cardiovascular disease: putting together the pieces of a complicated puzzle / G. Michas, R. Micha, A. Zampelas // Atherosclerosis. – 2014. – Vol. 234, Issue 2. – P. 320–328. https://doi.org/10.1016/j.atherosclerosis.2014.03.013

 

4. Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice : a key role for triglyceride metabolism / O. Rom, C. Grajeda-Iglesias, M. Najjar et al. // J. of Nutritional Biochem. – 2017. – Vol. 45. – P. 24–38. https://doi.org/10.1016/j.jnutbio.2017.02.023 

 

5. Rom, O. It is not just lipids: proatherogenic vs. antiatherogenic roles for amino acids in macrophage foam cell formation / O. Rom, M. Aviram // Current Opinion in Lipidol. – 2017. – Vol. 28, Issue 1. – P. 85–87.

 

6. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice / Y. Zhao, X. Y. Dai et al. // Acta Pharmacologica Sinica. – 2016. – Vol. 37, Issue 2. – P. 196–203. https://doi.org/10.1038/aps.2015.88 

 

7. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events / S. H. Shah, J. R. Bain, M. J. Muehlbauer et al. // Circ Cardiovasc. Genet. – 2010. – Vol. 3, Issue 2. – P. 207–214. https://doi.org/10.1161/circgenetics.109.852814 

 

8. Gannon, N. P. BCAA metabolism and insulin sensitivity – dysregulated by metabolic status? / N. P. Gannon, J. K. Schnuck, R. A. Vaughan // Molecular Nutrition & Food Res. – 2018. – Vol. 62, Issue 6. – Р. 170076–1700770. https://doi.org/10.1002/mnfr.201700756 

 

9. Human gut microbes impact host serum metabolome and insulin sensitivity / H. K. Pedersen, V. Gudmundsdottir, H. B. Nielsen et al. // Nature. – 2016. – Vol. 535, Issue 7612. – P. 376–381.

 

10. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance / C. B. Newgard, J. An, J. R. Bain et al. // Cell Metab. – 2009. – Vol. 9, Issue 4. – P. 311–326. https://doi.org/10.1016/j.cmet.2009.02.002 

 

11. Bifari, F. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals : a pharmacological point of view / F. Bifari,E. Nisoli// British J. of Pharmacol. – 2017. – Vol. 174, Issue 11. – P. 1366–1377. https://doi.org/10.1111/bph.13624 

 

12. Association of circulating branched-chain amino acids with cardiometabolic traits differs between adults and the oldest-old / L. Sun, C. Hu, R. Yang et al. // Oncotarget. – 2017. – Vol. 8, Issue 51. – P. 88882–88893. https://doi.org/10.18632/oncotarget.21489 

 

13. Effects of amino acid supplementation on myocardial cell damage and cardiac function in diabetes / T. S. Paramjit, James Thliveris et al. // Experimental & Clinical Cardiol. – 2011. – Vol. 16, Issue 3. – P. 17–22.

 

14. Ito, T. The potential usefulness of taurine on diabetes mellitus and its complications / T. Ito, S. W. Schaffer, J. Azuma // Amino Acids. – 2011. – Vol. 42, Issue 5. – P. 1529–1539. https://doi.org/10.1007/s00726-011-0883-5 

 

15. Endogenous antioxidants and radical scavengers / A. M. Rizzo, P. Berselli, S. Zava et al. // Advances in Experimental Medicine and Biol. – 2011. – Vol. 698. – P. 52–67. https://doi.org/10.1007/978-1-4419-7347-4_5

 

16. Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction / T. A. Clark, T. G. Maddaford, P. S. Tappia et al. // Current Pharmaceutical Biotechnol. – 2010. – Vol. 11, Issue 8. – P. 906–910. https://doi.org/10.2174/138920110793261999 

 

17. Lieberman, Harris R. Amino Acid and Protein Requirements : Cognitive Performance, Stress, and Brain Function / Harris R. Lieberman // Protein and Amino Acids. – 1999. – P. 289–307.

 

18. Nikolic, J. Effect of caffeine on metabolism of L-arginine in the brain / J. Nikolic, G. Bjelakovic, I. Stojanovic // Guanidino Compounds in Biology and Medicine. – 2003. – Vol. 244, Issue 1–2. – P. 125–128. https://doi.org/10.1007/978-1-4615-0247-0_18 

 

19. The effects of L-arginine on neurological function, histopathology, and expression of hypoxia-inducible factor-1 alpha following spinal cord ischemia in rats / M. C. Tuncer, E. S. Hatipoglu, H. Ozturk et al. // Eur. Surgical Res. – 2005. – Vol. 37, Issue 6. – P. 323–329. https://doi.org/10.1159/000090331 

 

20. Global arginine bioavailability ratio is decreased in patients with major depressive disorder / Toni Ali-Sisto, Tommi Tolmunen, HeimoViinamäki et al. // J. of Affective Disorders. – 2018. – Vol. 229. – P. 145–151 https://doi.org/10.1016/j.jad.2017.12.030 

 

21. Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research / Y. Koga, N. Povalko, E. Inoue et al. // J. Neurol. – 2018. – Vol. 265, Issue 12. – P. 2861–2874. https://doi.org/10.1007/s00415-018-9057-7 

 

22. A metabolomic approach to identifying biomarkers in blood of Alzheimer’s disease / Chia Ni Lin, Chin Chang Huang et al. // Annals of Clinical and Translational Neurol. – 2019. – Vol. 6, Issue 3. – P. 537–545. https://doi.org/10.1002/acn3.726 

 

23. What success can teach us about failure : the plasma metabolome of older adults with superior memory and lessons for Alzheimer’s disease / M. Mapstone, F. Lin, M. A. Nalls et al. // Neurobiol. Aging. – 2017. – Vol. 51. – P. 148–155. https://doi.org/10.1016/j.neurobiolaging.2016.11.007

 

24. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD / C. A. Colton, R. T. Mott, H. Sharpe et al. // J. of Neuroinflammation. – 2006. – Vol. 3. – P. 1–27. https://doi.org/10.1186/1742-2094-3-27 

 

25. Altered arginine metabolism in Alzheimer’s disease brains / P. Liu, M. S. Fleete, Y. Jing et al. // Neurobiol. Aging. – 2014. – Vol. 35, Issue 9. – P. 1992–2003. https://doi.org/10.1016/j.neurobiolaging.2014.03.013 

 

26. Arginine deprivation and immune suppression in a mouse model of Alzheimer’s disease / M. J. Kan, J. E. Lee, J. G. Wilson et al. // J. of Neuroscie. – 2015. – Vol. 35 – P. 5969–5982. https://doi.org/10.1523/jneurosci.4668-14.2015

 

27. Excitatory amino acids and multiple sclerosis: Evidence from cerebrospinal fluid / P. Sarchielli, L. Greco, A. Floridi et al. // Archives of Neurol. – 2003. – Vol. 60, Issue 8. – P. 1082–1088. https://doi.org/10.1001/archneur.60.8.1082 

 

28. Gawwam, G. A. Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis / G. A. Gawwam, I. K. Sharquie // Sci. World J. – 2017. – P. 5. https://doi.org/10.1155/2017/9320802 

 

29. Integrated Lipidomics and Metabolomics Analysis of Tears in Multiple Sclerosis: An Insight into Diagnostic Potential of Lacrimal Fluid / Ilaria Cicalini, Claudia Rossi, Damiana Pieragostino et al. // Intern. J. of Molecular Sci. – 2019. – Vol. 20, Issue 6. – P. 1265. https://doi.org/10.3390/ijms20061265 

 

30. Toward a Glutamate Hypothesis of Frontotemporal Dementia / Alberto Benussi, Antonella Alberici, Emanuele Buratti et al. // Front Neurosci. – 2019. – Vol. 13. – P. 304. https://doi.org/10.3389/fnins.2019.00304 

 

31. Kawaguchi, T. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis / T. Kawaguchi,E. Taniguchi, M. Sata // Nutrition in Clinical Practice. – 2013. – Vol. 28, Issue 5. – P. 580–588. https://doi.org/10.1177/0884533613496432 

 

32. Branched-chain amino acids for people with hepatic encephalopathy / L. L. Gluud, G. Dam, I. Les et al. // Cochrane Database of Systematic Rev. – 2017. – Issue 2. https://doi.org/10.1002/14651858.cd001939.pub4 

 

33. Branched-сhain аmino аcids рrevent hepatocarcinogenesis and prolong survival of patients with cirrhosis / Takumi Kawaguchi, Koichi Shiraishi, Toshifumi Ito et al. // Clinical Gastroenterol. and Hepatol. – 2014. – Vol. 12, Issue 6. – P. 1012–1018. https://doi.org/10.1016/j.cgh.2013.08.050 

 

34. Hagiwara, A. Branched-chain amino acids prevent insulin-induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2-dependent mechanisms / A. Hagiwara, M. Nishiyama, S. Ishizaki // J. of Cellular Physiol. – 2012. – Vol. 227, Issue 5. – P. 2097–2105. https://doi.org/10.1002/jcp.22941 

 

35. Altered amino acid concentrations in NAFLD : Impact of obesity and insulin resistance / M. Gaggini, F. Carli, C. Rosso et al. // Hepatology. – 2018. – Vol. 67, Issue 1. – P. 145–158. https://doi.org/10.1002/hep.29465 





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