Quantification and evaluation of plasma free amino acid concentrations by LC-MS/MS after total gastrectomy

Year 2024, Volume: 11 Issue: 4, 1605 - 1622

Tuğrul Çağrı Akman , Yücel Kadıoğlu , Burak Bayrak , Mehmet İlhan Yıldırgan , Esra Dişçi

https://doi.org/10.18596/jotcsa.1529042

Abstract

The effect of total gastrectomy (TG) on plasma free amino acid (PFAA) concentrations in patients with stage II gastric cancer was investigated in the study. Nineteen patients' plasma samples were collected before and three months post-gastrectomy, and PFAA levels were quantified using LC-MS/MS. For gradient elution of amino acids, the mobile phases (A: 3% formic acid-5% methanol-30 mM ammonium formate, B: acetonitrile) and a Hypersil C18 column (100 mm x 2.1 m, 1.9 µm) were used. The findings revealed substantial modifications in the profile of PFAA after TG. In particular, the concentrations of twenty amino acids increased significantly, including branched-chain amino acids, L-glutamate, L-alanine, L-methionine, glycine, L-cystine, and L-histidine. Conversely, L-arginine was also reduced statistically. These alterations in the PFAA profile indicate the favorable effects of TG on various physiological processes, such as enhanced immune function, improved tissue healing, and increased energy production. Investigating the effects of various surgical techniques on PFAA profiles is a promising approach for optimizing surgical procedures, improving metabolic function, increasing immunological responses, and improving overall quality of life. These findings highlight the significance of evaluating amino acid metabolism as an important part of treatment, given its potential to improve clinical outcomes and general well-being.

Keywords

Amino acids, Total gastrectomy, Gastric cancer, LC-MS/MS

Ethical Statement

Ethical approval was obtained from the Atatürk University Faculty of Non-invasive Clinical Research Ethics Committee on March 29, 2024, under the permit number B.30.2.ATA.0.01.00/244.

Thanks

The authors are grateful to Atatürk University and Erzincan Binali Yildirim University for support of this study.

References

• 1. Goh YM, Gillespie C, Couper G, Paterson-Brown S. Quality of life after total and subtotal gastrectomy for gastric carcinoma. Surg [Internet]. 2015 Oct 1;13(5):267–70. Available from: <URL>.
• 2. Sexton RE, Al Hallak MN, Diab M, Azmi AS. Gastric cancer: A comprehensive review of current and future treatment strategies. Cancer Metastasis Rev [Internet]. 2020 Dec 7;39(4):1179–203. Available from: <URL>.
• 3. Svedlund J, Sullivan M, Liedman B, Lundell L. Long term consequences of gastrectomy forpatients’ quality of life: The impact of reconstructive techniques. Am J Gastroenterol [Internet]. 1999 Feb;94(2):438–45. Available from: <URL>.
• 4. Schölmerich J. Postgastrectomy syndromes—diagnosis and treatment. Best Pract Res Clin Gastroenterol [Internet]. 2004 Oct 1;18(5):917–33. Available from: <URL>.
• 5. Poitou Bernert C, Ciangura C, Coupaye M, Czernichow S, Bouillot JL, Basdevant A. Nutritional deficiency after gastric bypass: Diagnosis, prevention and treatment. Diabetes Metab [Internet]. 2007 Feb 1;33(1):13–24. Available from: <URL>.
• 6. Mayers JR, Wu C, Clish CB, Kraft P, Torrence ME, Fiske BP, et al. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med [Internet]. 2014 Oct 28;20(10):1193–8. Available from: <URL>.
• 7. Öztürk Er E, Erarpat S, Bodur S, Günkara ÖT, Özbek B, Bakırdere S. Accurate determination of amino acids by quadruple isotope dilution-reverse phase liquid Chromatography-Tandem mass spectrometry after derivatization with 2-Naphthoyl chloride. J Chromatogr A [Internet]. 2022 Mar 29;1667:462870. Available from: <URL>.
• 8. Mondanelli G, Iacono A, Carvalho A, Orabona C, Volpi C, Pallotta MT, et al. Amino acid metabolism as drug target in autoimmune diseases. Autoimmun Rev [Internet]. 2019 Apr 1;18(4):334–48. Available from: <URL>.
• 9. Rondanelli M, Opizzi A, Antoniello N, Boschi F, Iadarola P, Pasini E, et al. Effect of essential amino acid supplementation on quality of life, Amino acid profile and strength in institutionalized elderly patients. Clin Nutr [Internet]. 2011 Oct 1;30(5):571–7. Available from: <URL>.
• 10. Manig F, Kuhne K, von Neubeck C, Schwarzenbolz U, Yu Z, Kessler BM, et al. The why and how of amino acid analytics in cancer diagnostics and therapy. J Biotechnol [Internet]. 2017 Jan 20;242:30–54. Available from: <URL>.
• 11. Bi X, Henry CJ. Plasma-free amino acid profiles are predictors of cancer and diabetes development. Nutr Diabetes [Internet]. 2017 Mar 13;7(3):e249. Available from: <URL>.
• 12. Atila A, Alay H, Yaman ME, Akman TC, Cadirci E, Bayrak B, et al. The serum amino acid profile in COVID-19. Amino Acids [Internet]. 2021 Oct 4;53(10):1569–88. Available from: <URL>.
• 13. Erawijantari PP, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, et al. Influence of gastrectomy for gastric cancer treatment on faecal microbiome and metabolome profiles. Gut [Internet]. 2020 Aug 1;69(8):1404–15. Available from: <URL>.
• 14. Tatara MR, Śliwa E, Krupski W, Worzakowska M. 3-Hydroxy-3-methylbutyrate administration diminishes fundectomy-induced osteopenia of the lumbar spine in pigs. Nutrition [Internet]. 2008 Jul 1;24(7–8):753–60. Available from: <URL>.
• 15. Tatara MR, Krupski W, Szpetnar M, Dąbrowski A, Bury P, Szabelska A, et al. Effects of total gastrectomy on plasma silicon and amino acid concentrations in men. Exp Biol Med [Internet]. 2015 Dec 2;240(12):1557–63. Available from: <URL>.
• 16. Aquilani R, Maestri R, Boselli M, Achilli MP, Arrigoni N, Bruni M, et al. The relationship between plasma amino acids and circulating albumin and haemoglobin in postabsorptive stroke patients. Clelland JD, editor. PLoS One [Internet]. 2019 Aug 14;14(8):e0219756. Available from: <URL>.
• 17. Package “ggpubr” type package title “ggplot2” based publication ready plots [Internet]. [cited 2024 May 18]. Available from: <URL>.
• 18. Gwin JA, Church DD, Wolfe RR, Ferrando AA, Pasiakos SM. Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit. Nutrients [Internet]. 2020 Aug 15;12(8):2457. Available from: <URL>.
• 19. Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab (Lond) [Internet]. 2018 Dec 3;15(1):33. Available from: <URL>.
• 20. Wu G. Amino acids: Metabolism, functions, and nutrition. Amino Acids [Internet]. 2009 May 20;37(1):1–17. Available from: <URL>.
• 21. Wu G, Lupton JR, Turner ND, Fang YZ, Yang S. Glutathione metabolism and its implications for health. J Nutr [Internet]. 2004 Mar 1;134(3):489–92. Available from: <URL>.
• 22. Cheng X, Xu HD, Ran HH, Liang G, Wu FG. Glutathione-depleting nanomedicines for synergistic cancertherapy. ACS Nano [Internet]. 2021 May 25;15(5):8039–68. Available from: <URL>.
• 23. Kumar M, Ji B, Babaei P, Das P, Lappa D, Ramakrishnan G, et al. Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling. Metab Eng [Internet]. 2018 Sep 1;49:128–42. Available from: <URL>.
• 24. Nagahama S, Korenaga D, Honda M, Inutsuka S, Sugimachi K. Assessment of the intestinal permeability after a gastrectomy and the oral administration of anticancer drugs in rats: Nitric oxide release in response to gut injury. Surgery [Internet]. 2002 Jan 1;131(1):S92–7. Available from: <URL>.
• 25. Luise D, Chalvon-Demersay T, Correa F, Bosi P, Trevisi P. Review: A systematic review of the effects of functional amino acids on small intestine barrier function and immunity in piglets. animal [Internet]. 2023 Jun 1;17:100771. Available from: <URL>.
• 26. Shynkevych VI, Kolomiiets S V., Kaidashev IP. Effects of l-arginine and l-ornithine supplementations on the treatment of chronic periodontitis: A preliminary randomized short-term clinical trial. Heliyon [Internet]. 2021 Nov 1;7(11):e08353. Available from: <URL>.
• 27. O’Riordain M. Effect of glutamine on immune function in the surgical patient. Nutrition [Internet]. 1996 Dec 1;12(12):S82–4. Available from: <URL>.
• 28. Chinkes DL. Methods for measuring tissue protein breakdown rate in vivo. Curr Opin Clin Nutr Metab Care [Internet]. 2005 Sep;8(5):534–7. Available from: <URL>.
• 29. Demopoulos C, Antonopoulou S, Theoharides TC. COVID‐19, microthromboses, inflammation, and platelet activating factor. BioFactors [Internet]. 2020 Nov 9;46(6):927–33. Available from: <URL>.