Abstract
Background: Investigation of the direct link between l-carnitine (LC), a quaternary ammonium compound that facilitates the passage of unsaturated fatty acids into the mitochondrial matrix, and free calcium (Ca2+) is needed to explain a number of varying results obtained from different in vitro and in vivo studies of LC as a supplement.
Methods: The chemical structure of LC, which contains oxygen ligand atoms, prompted to measure its activity as a Ca2+ chelator. The measurement was carried out spectrophotometrically by measuring the reduction in the formation of Ca2+-o-cresolphthalein complexone (Ca-CPC) in the presence of different doses of LC (0.075, 0.75, and 7.5 mM) compared to the control (0.0 mM LC).
Results: The effect of LC was measured as a free entity in solution and when added to human serum. Our results showed a significant decrease (p<0.05) in the average absorbance of Ca-CPC in the presence of LC compared to the control.
Conclusions: In conclusion, LC exhibits a significant Ca2+ chelating activity. As Ca2+ is vital in the biochemical and physiological processes of living cells, LC could be affecting the calcium-dependent biological systems by limiting the levels of free Ca2+. Examples include decelerating the blood clotting process, amplifying the effect of anticoagulants, reducing nitric oxide synthase activity, inhibiting platelet aggregation, and decreasing sperm motility.
Acknowledgments
This work is supported by both Jordan University of Science and Technology (grant number 20120135) and Cleveland State University.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
References
1. Bach AC. Carnitine in human nutrition. Z Ernahrungswiss 1982;21:257–65.10.1007/BF02020743Search in Google Scholar PubMed
2. Steiber A, Kerner J, Hoppel CL. Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 2004;25:455–73.10.1016/j.mam.2004.06.006Search in Google Scholar PubMed
3. Silva-Adaya D, Perez-De La Cruz V, Herrera-Mundo MN, Mendoza-Macedo K, Villeda-Hernández J, Binienda Z, et al. Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of L-carnitine. J Neurochem 2008;105:677–89.10.1111/j.1471-4159.2007.05174.xSearch in Google Scholar PubMed
4. Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. J Agric Food Chem 2004;52:7970–81.10.1021/jf048741xSearch in Google Scholar PubMed
5. Vanella A, Russo A, Acquaviva R, Campisi A, Di Giacomo C, Sorrenti V, et al. L-propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol 2000;16:99–104.10.1023/A:1007638025856Search in Google Scholar
6. Gulcin I. Antioxidant and antiradical activities of L-carnitine. Life Sci 2006;78:803–11.10.1016/j.lfs.2005.05.103Search in Google Scholar PubMed
7. Yuan YV, Carrington MF, Walsh NA. Extracts from dulse (Palmaria palmata) are effective antioxidants and inhibitors of cell proliferation in vitro. Food Chem Toxicol 2005;43:1073–81.10.1016/j.fct.2005.02.012Search in Google Scholar PubMed
8. Lindsay R. Food additives. In: Fennema OR, editor. Food chemistry. New York: Marcel Dekker Inc., 1996.Search in Google Scholar
9. Devlin T. Textbook of biochemistry with clinical correlations, 7th ed. Hoboken: Wiley, 2011.Search in Google Scholar
10. Weiss HJ, Lages B. Platelet prothrombinase activity and intracellular calcium responses in patients with storage pool deficiency, glycoprotein IIb-IIIa deficiency, or impaired platelet coagulant activity – a comparison with Scott syndrome. Blood 1997;89:1599–611.10.1182/blood.V89.5.1599Search in Google Scholar
11. Mathur A, Zhong D, Sabharwal AK, Smith KJ, Bajaj SP. Interaction of factor IXa with factor VIIIa. Effects of protease domain Ca2+ binding site, proteolysis in the autolysis loop, phospholipid, and factor X. J Biol Chem 1997;272:23418–26.10.1074/jbc.272.37.23418Search in Google Scholar PubMed
12. Hakeshzadeh F, Tabibi H, Ahmadinejad, Malakoutian T, Hedayati M. Effects of L-Carnitine supplement on plasma coagulation and anticoagulation factors in hemodialysis patients. Ren Fail 2010;32:1109–14.10.3109/0886022X.2010.510617Search in Google Scholar PubMed
13. Pignatelli P, Lenti L, Sanguigni V, Frati G, Simeoni I, Gazzaniga PP, et al. Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress. Am J Physiol Heart Circ Physiol 2003;284:H41–8.10.1152/ajpheart.00249.2002Search in Google Scholar
14. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385.Search in Google Scholar
15. Nei M, Ngo L, Sirven JI, Sperling MR. Ketogenic diet in adolescents and adults with epilepsy. Seizure 2014. (doi: 10.1016/j.seizure.2014.02.015).Search in Google Scholar
16. De Vivo DC, Bohan TP, Coulter DL, Dreifuss FE, Greenwood RS, Nordli DR Jr, et al. L-carnitine supplementation in childhood epilepsy: current perspectives. Epilepsia 1998;39:1216–25.10.1111/j.1528-1157.1998.tb01315.xSearch in Google Scholar
17. Kossoff EH, Zupec-Kania BA, Rho JM. Ketogenic diets: an update for child neurologists. J Child Neurol 2009;24:979–88.10.1177/0883073809337162Search in Google Scholar
18. Bergqvist AG, Schall JI, Stallings VA, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr 2008;88:1678–84.10.3945/ajcn.2008.26099Search in Google Scholar
19. Berry-Kravis E, Booth G, Sanchez AC, Woodbury-Kolb J. Carnitine levels and the ketogenic diet. Epilepsia 2001;42:1445–51.10.1046/j.1528-1157.2001.18001.xSearch in Google Scholar
20. Koeck T, Kremser K. l-Carnitine alters nitric oxide synthase activity in fibroblasts depending on the peroxisomal status. Int J Biochem Cell Biol 2003;35:149–56.10.1016/S1357-2725(02)00183-8Search in Google Scholar
21. Hong CY, Chiang BN, Wu P, Wei YH, Fong JC. Involvement of calcium in the caffeine stimulation of human sperm motility. Br J Clin Pharmacol 1985;19:739–43.10.1111/j.1365-2125.1985.tb02708.xSearch in Google Scholar
22. Brokaw CJ. Regulation of sperm flagellar motility by calcium and cAMP-dependent phosphorylation. J Cell Biochem 1987;35:175–84.10.1002/jcb.240350302Search in Google Scholar
23. Magnus O, Abyholm T, Kofstad J, Purvis K. Ionized calcium in human male and female reproductive fluids: relationships to sperm motility. Hum Reprod 1990;5:94–8.10.1093/oxfordjournals.humrep.a137049Search in Google Scholar
24. Fakih H, MacLusky N, DeCherney A, Wallimann T, Huszar G. Enhancement of human sperm motility and velocity in vitro: effects of calcium and creatine phosphate. Fertil Steril 1986;46:938–44.10.1016/S0015-0282(16)49839-0Search in Google Scholar
25. Meseguer M, Garrido N, Martinez-Conejero JA, Simon C, Pellicer A, Remohi J. Relationship between standard semen parameters, calcium, cholesterol contents, and mitochondrial activity in ejaculated spermatozoa from fertile and infertile males. J Assist Reprod Genet 2004;21:445–51.10.1007/s10815-004-8761-7Search in Google Scholar PubMed PubMed Central
26. Banihani S, Sharma R, Bayachou M, Sabanegh E, Agarwal A. Human sperm DNA oxidation, motility and viability in the presence of l-carnitine during in vitro incubation and centrifugation. Andrologia 2012;44:505–12.10.1111/j.1439-0272.2011.01216.xSearch in Google Scholar PubMed
27. Deana R, Rigoni F, Francesconi M, Cavallini L, Arslan P, Siliprandi N. Effect of l-carnitine and l-aminocarnitine on calcium transport, motility, and enzyme release from ejaculated bovine spermatozoa. Biol Reprod 1989;41:949–55.10.1095/biolreprod41.5.949Search in Google Scholar PubMed
28. Stapleton S, Currie R, Scott R, Bell B. Palmitoyl-DL-carnitine has calcium-dependent effects on cultured neurones from rat dorsal root ganglia. Br J Pharmacol 1992 207:1192–7.10.1111/j.1476-5381.1992.tb13427.xSearch in Google Scholar PubMed PubMed Central
29. Patel MK, Economides AP, Byrne NG. Effects of palmitoyl carnitine on perfused heart and papillary muscle. J Cardiovasc Pharmacol Ther 1999;4:85–96.10.1177/107424849900400203Search in Google Scholar PubMed
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