Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Chemoreactomic analysis of citrulline malate molecules

Full Text:


Citrulline malate that is essential for the biosynthesis of arginine promotes dehydration of ammonium endotoxins, by participating in the urea cycle. The indications for the use of citrulline malate are functional asthenia, asthenic syndrome, overfatigue, increased fatigue, and rehabilitation during recovery following diseases.

Objective: to simulate the biological properties of citrulline malate.

Material and methods. Reliable estimates of more than 2,500 biological activities were obtained for this molecule, which were compared with those of the reference molecules of acetylcarnitine and meldonium.

Results and discussion. The data obtained from chemoreactome simulation may suggest that there are substantial differences between the pharmacological effects of citrulline malate and the reference molecules. Malate anion as a component of citrulline malate significantly enhances the absorption of citrulline molecules in the gastrointestinal tract regardless of gastric acidity. Citrulline malate improves renal bicarbonate anion absorption, which contributes to the overcoming of acidosis. The results of chemoreactome simulation indicate that citrulline malate has antidepressant, anxiolytic, and anti-inflammatory properties, which can make a substantial contribution to the development of anti-asthenic and detoxifying effects of the drug. Citrulline malate can also show anticoagulant, antivasopressor, hypoglycemic, antihypercholesterolemic, and antimicrobial effects. These properties of citrulline malate can contribute to the earliest recovery of patients after asthenia or intensive strenuous exercises as compared to those of the reference molecules (meldonium, acetylcarnitine).

Conclusion. The findings are consistent with the available experimental and clinical data and are indicative of promising clinical applications of citrulline malate. 

About the Authors

I. Yu. Torshin
Moscow Institute of Physics and Technology, Dolgoprudnyi, Moscow Region
Russian Federation
9, Institutsky Lane, Dolgoprudnyi, Moscow Region 141700

O. A. Gromova
Ivanovo State Medical Academy, Ministry of Health of Russia, Ivanovo
Russian Federation
8, Sheremetevsky Passage., Ivanovo 153000

L. E. Fedotova
Ivanovo State Medical Academy, Ministry of Health of Russia, Ivanovo
Russian Federation
8, Sheremetevsky Passage., Ivanovo 153000

A. N. Gromov
Federal Research Center of Informatics and Management, Russian Academy of Sciences, Moscow
Russian Federation
44/2, Vavilov St., Moscow 119333

K. V. Rudakov
Moscow Institute of Physics and Technology, Dolgoprudnyi, Moscow Region
Russian Federation
9, Institutsky Lane, Dolgoprudnyi, Moscow Region 141700


1. Bendahan D, Mattei JP, Ghattas B, et al. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002 Aug;36(4):282-9.

2. Cox M, Lehninger AL, Nelson DR. Lehninger principles of biochemistry. 3rd edition. New York: Worth Publishers; 2000.

3. Callis A, Magnan de Bornier B, Serrano JJ, et al. Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Arzneimittelforschung. 1991 Jun;41(6):660-3.

4. Jensen A, Glenn J, Stone M, Gray M. Effect Of Acute Citrulline-malate Supplementation On Muscular Power: 896 Board #212 June 1, 3: 30 PM – 5: 00 PM. Med Sci Sports Exerc. 2016 May;48(5 Suppl 1):252. doi: 10.1249/01.mss.0000485759.38927.5f.

5. Glenn JM, Gray M, Jensen A, et al. Acute Citrulline-Malate Supplementation Increases Strength and Endurance During Isokinetic Exercise in Masters-Aged Female Tennis Players: 894 Board #210 June 1, 3: 30 PM – 5: 00 PM. Med Sci Sports Exerc. 2016 May;48(5 Suppl 1):251-2. doi: 10.1249/01.mss.0000485757. 31118.50.

6. Glenn JM, Gray M, Jensen A, et al. Acute citrulline-malate supplementation improves maximal strength and anaerobic power in female, masters athletes tennis players. Eur J Sport Sci. 2016 Nov;16(8):1095-103. doi: 10.1080/17461391.2016.1158321. Epub 2016 Mar 28.

7. Cunniffe B, Papageorgiou M, O'Brien B, et al. Acute Citrulline-Malate Supplementation and High-Intensity Cycling Performance. J Strength Cond Res. 2016 Sep;30(9):2638-47. doi: 10.1519/JSC.0000000000001338.

8. Torshin IYu, Rudakov KV. 2014. On the application of the combinatorial theory of solvability to the analysis of chemographs. Part 1: Fundamentals of modern chemical bonding theory and the concept of the chemograph. Pattern Recognit. Image Anal. 2014;24(1):11-23.

9. Torshin IYu, Rudakov KV. On the application of the combinatorial theory of solvability to the analysis of chemographs: Part 2. Local completeness of invariants of chemographs in view of the combinatorial theory of solvability. Pattern Recognit. Image Anal. 2014;24(2):196-208.

10. Рудаков КВ, Торшин ИЮ. Об отборе информативных значений признаков на базе критериев разрешимости в задаче распознавания вторичной структуры белка. ДАН. 2011;441(1):1-5. [Rudakov KV, Torshin IYu. On the selection of informative characteristic values on the basis of criteria of solvability in the problem of protein secondary structure recognition. DAN. 2011;441(1):1-5. (In Russ.)].

11. Torshin IYu. On solvability, regularity, and locality of the problem of genome annotation. Pattern Recognition and Image Analysis. 2010;20(3):386-95.

12. Журавлёв ЮИ, Рудаков КВ, Торшин ИЮ. Алгебраические критерии локальной разрешимости и регулярности как инструмент исследования морфологии аминокислотных последовательностей. Труды МФТИ. 2011;3(4):67-76. [Zhuravlev YuI, Rudakov KV, Torshin IYu. Algebraic criteria for local solvability and regularity as a tool to investigate the morphology of amino acid sequences. Trudy MFTI. 2011;3(4):67-76. (In Russ.)].

13. Журавлев ЮИ. Об алгебраическом подходе к решению задач распознавания или классификации. Проблемы кибернетики. 1978;(33):5-68. [Zhuravlev YuI. About algebra￾ic approach to solving the problems of recognition or classification. Problemy kibernetiki. 1978;(33):5-68. (In Russ.)].

14. Bolton E, Wang Y, Thiessen PA, Bryant SH. PubChem: Integrated Platform of Small Molecules and Biological Activities. In: Annual Reports in Computational Chemistry. Volume 4. Washington, DC: American Chemical Society; 2008.

15. Wishart DS, Tzur D, Knox C, et al. HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007 Jan;35(Database issue):D521-6.

16. Torshin IYu. Bioinformatics in the post-genomic era: sensing the change from molecular genetics to personalized medicine. New-York: Nova Biomedical Books; 2009.

17. Торшин ИЮ, Громова ОА. Экспертный анализ данных в молекулярной фармакологии. Москва: Издательство МЦНМО; 2012. 768 с. [Torshin IYu, Gromova OA. Ekspertnyi analiz dannykh v molekulyarnoi farmakologii [Expert data analysis in molecular pharmacology]. Moscow: Izdatel'stvo MTsNMO; 2012. 768 p.].

18. Torshin IYu. Bioinformatics in the post-genomic era: physiology and medicine. New-York: Nova Biomedical Books; 2007.

19. Piascik MT, Perez DM. Alpha1-adrenergic receptors: new insights and directions. J Pharmacol Exp Ther. 2001 Aug;298(2):403-10.

20. Boron WF, Boulpaep EL. Medical Physiology: A Cellular and Molecular Approach.N.-Y.: Saunders; 2012. 1352 p.

21. Carboni E, Tanda GL, Frau R, Di Chiara G. Blockade of the noradrenaline carrier increases extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken up in vivo by noradrenergic terminals. J Neurochem. 1990 Sep;55(3):1067-70.

22. Girault JA, Greengard P. The neurobiology of dopamine signaling. Arch Neurol. 2004 May; 61(5):641-4.

23. Nelson DL. 5-HT5 receptors. Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):53-8.

24. Tham A, Jonsson U, Andersson G, et al. Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder – A systematic review and a meta-analysis. J Affect Disord. 2016 Nov 15;205:1-12. doi: 10.1016/j.jad.2016.06.013. Epub 2016 Jun 18.

25. Park CH, Yong A, Lee SH. Involvement of selective alpha-2 adrenoreceptor in sympathetically maintained pain. J Korean Neurosurg Soc. 2010 Jun;47(6):420-3. doi: 10.3340/jkns.2010.47.6.420. Epub 2010 Jun 30.

26. Harkanen L, Halonen J, Selander T, Kokki H. Beta-adrenergic antagonists during general anesthesia reduced postoperative pain: a systematic review and a meta-analysis of randomized controlled trials. J Anesth. 2015 Dec;29(6):934-43. doi: 10.1007/s00540-015- 2041-9. Epub 2015 Jul 10.

27. Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May; 8(5):781-97. doi: 10.1586/14737175.8.5.781.

28. Crisp T, Stafinsky JL, Spanos LJ, et al. Analgesic effects of serotonin and receptorselective serotonin agonists in the rat spinal cord. Gen Pharmacol. 1991;22(2):247-51.

29. Moscarello MA, Lei H, Mastronardi FG, et al. Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis. Dis Model Mech. 2013 Mar;6(2):467-78. doi: 10.1242/dmm.010520. Epub 2012 Nov 1.

30. Knight JS, Subramanian V, O'Dell AA, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann Rheum Dis. 2015 Dec;74(12):2199-206. doi: 10.1136/annrheumdis- 2014-205365. Epub 2014 Aug 7.

31. Harvey JM, Broderick G, Bowie A, et al. Tracking post-infectious fatigue in clinic using routine Lab tests. BMC Pediatr. 2016 Apr 26;16:54. doi: 10.1186/s12887-016-0596-8.

32. Astrom E, Friman G, Pilstrom L. Effects of viral and mycoplasma infections on ultrastructure and enzyme activities in human skeletal muscle. Acta Pathol Microbiol Scand A. 1976 Mar;84(2):113-22.

For citation:

Torshin I.Yu., Gromova O.A., Fedotova L.E., Gromov A.N., Rudakov K.V. Chemoreactomic analysis of citrulline malate molecules. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(2):30-35. (In Russ.)

Views: 453

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)