Indian Journal of Medical Biochemistry

Register      Login

VOLUME 27 , ISSUE 2 ( May-August, 2023 ) > List of Articles


Beneficiary Effect of Zinc Supplementation in Tuberculosis as Reflected by Serum Level of Diagnostic Biomolecules

Dipak Kumar Chattopadhyay

Keywords : Cholinesterase, Extrapulmonary tuberculosis, Glutamine synthetase, Metallothioneins, Pulmonary tuberculosis, Superoxide dismutase, Zinc transporters, Zrt-Irt-related proteins

Citation Information : Chattopadhyay DK. Beneficiary Effect of Zinc Supplementation in Tuberculosis as Reflected by Serum Level of Diagnostic Biomolecules. Indian J Med Biochem 2023; 27 (2):33-39.

DOI: 10.5005/jp-journals-10054-0221

License: CC BY-NC 4.0

Published Online: 20-01-2024

Copyright Statement:  Copyright © 2023; The Author(s).


Aim and objective: This author had indoctrinated a higher Mycobacterium tuberculosis (Mtb) origin serum superoxide dismutase (SOD), detectable Mtb origin serum glutamine synthetase (GS) and inhibited host origin serum cholinesterase (ChE) as diagnostics for tuberculosis (TB). Mycobacterium tuberculosis by secreting abundant siderophores, the Fe+3 chelators, scavenges iron (Fe) from transferrin, lactoferrin, etc.; and thus, major decompartmentalized state of Fe takes place in host tissues, generation of superoxides is accentuated, which are used up by Mtb for dismutation reaction to evolve soluble oxygen for survival of this obligatory aerobe. Zinc (Zn), a redox inert metal, accelerates reversion to normal compartmentalized state of Fe by replacing Fe from thiol group binding site. Zn, by decreasing generation of reactive oxygen species renders an onslaught on Mtb. In this study, the author had mulled the effect of Zn supplementation (25 mgm of elemental Zn daily orally for 1 month) on the serum level of TB diagnostics as mentioned. Materials and methods: Serum SOD, GS, and ChE were assayed for TB patients at baseline and also after 1 month with anti-TB drugs as two groups; one without and other with Zn supplementation. Same parameters were also measured for normal control and lung disease control subjects at baseline. Result: Significant decrease in serum SOD (p = 0.01) and GS (p = 0.01) in TB patients with Zn supplementation for 1 month had been recorded in comparison to those without Zn supplementation. Also, recovery of serum ChE activity with Zn supplementation was significant (p = 0.002). Conclusion: With the assertive and veritable improvement by instituting Zn supplementation in TB patients as reflected by serum level of diagnostic parameters, it is a great solemnity to promulgate that oral Zn supplementation might be added to anti-TB (A-TB) drug regime for early onslaught on Mtb and also for an effective weapon preventing development of primary drug resistance.

  1. Churchyard GJ, Swindells S. Controlling latent TB tuberculosis infection in high burden countries: A neglected strategy to end TB. PLoS Med 2019;16(4):e1002787. DOI: 10.1371/journal.pmed.1002787.
  2. Chattopadhyay DK. Serum glutamine synthetase activity as biomarker for tuberculosis diagnosis and monitoring anti-tubercular drug therapy success. Indian J Biochem Biophys 2019;56(6):427–432. DOI: 10.56042/ijbb.v5616.29214.
  3. Chattopadhyay DK. Superoxide dismutase: A biomarker for early diagnosis of tuberculosis. J Clin Diagn Res 2019;13(7):BC01–BC03. DOI: 10.7860/JCDR/2019/35298.12968.
  4. Chattopadhyay DK. Decreased serum cholinesterase activity: A reliable diagnostic aid for tuberculosis. J Clin Diagn Res 2021;15(3):BC16–BC19. DOI: 10.7860/JCDR/2021/46501.14657.
  5. Chattopadhyay DK. Ratio of serum superoxide dismutase and whole blood glutathione peroxidase: A noteworthy parameter for tuberculosis diagnosis. Indian J Med Biochem 2021;25(3):100–104.
  6. Chattopadhyay DK. Assay of serum iron and TIBC: A preliminary study for survey shortlisting suspected tuberculosis patients. Indian J Med Biochem 2022;26(3):81–86.
  7. Kochanczyk T, Drozd A, Krezel A. Relationship between the architecture of zinc coordination and zinc binding affinity in proteins-insights into zinc regulation. Metallomics 2015;7(2):244–257. DOI: 10.1039/c4mt00094c.
  8. Andreini C, Bertini I. A bioinformatics view of zinc enzymes. J Inorg Biochem 2012;111:150–156. DOI: 10.1016/j.jinorgbio.2011.11.020.
  9. Barnett JP, Bindauer CA, Kassaar O, et al. Allosteric modulation of zinc speciation by fatty acids. Biochim Biophys Acta 2013;1830:5456–5464. DOI: 10.1016/j.bbagen.2013.05.028.
  10. Cousins RJ, Liuzzi JP, Lichten LA. Mammalian zinc transport, trafficking, and signals. J Biol Chem 2006;281:24085–24089. DOI: 10.1074/jbc.R600011200.
  11. Sekler I, Sensi SL, Hershfinkel M, et al. Mechanism and regulation of cellular zinc transport. Mol Med 2007;13(7–8):337–343. DOI: 10.2119/2007-00037.Sekler.
  12. Krezel A, Maret W. Different redox states of metallothionein/thionein in biological tissues. Biochem J 2007;402(3):551–558. DOI: 10.1042/BJ20061044.
  13. Liuzzi JP, Lichten La, Rivera S, et al. Interleukin-6 regulates the zinc transporter ZIP 14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci 2005;102(19):6843–6848. DOI: 10.1073/pnas.0502257102.
  14. Haase H, Rink L. Zinc signals and immune function. Biofactors 2014;40(1):27–40. DOI: 10.1002/biof.1114.
  15. Banci L, Bertini I, Ciofi-Baffoni S, et al. A new zinc-protein coordination site in intracellular metal trafficking: Solution structure of the Apo and Zn(II) forms of Znt A (46-118). J Mol Biol 2002;323(5):883–897. DOI:
  16. Hasse H, Rink L. Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr 2009;29:133–152. DOI: 10.1146/annurev-nutr-080508-141119.
  17. Ghosh S, Hayden MS. Celebrating 25 years of NF-kB research. Immunol Rev 2012;246(1):5–13. DOI: 10.1111/j.1600-065X.2012.01111.x.
  18. Von Bulow V, Dubben S, Engelhardt G, et al. Zinc-dependent suppression of TNF-α production is mediated by protein kinase A-induced inhibition of Raf-1, IkB Kinase β, and NF-kb. J Immunol 2007;179(6):4180–4186. DOI: 10.4049/jimmunol.179.6.4180.
  19. Chattopadhyay DK, Maity CR, Nag D. Level of serum iron and serum TIBC in the tubercular cases under anti-tubercular drug treatment with zinc supplementation. Ind Med Gaz 2005;CXXXIX(5):185–191.
  20. Chattopadhyay DK. Zinc supplementation combats tuberculosis by reverting back to normal compartmentalized state of iron and hence increasing blood hemoglobin concentration. Indian J Med Biochem 2022;26(1):20–25. DOI: 10.5005/jp-journals-10054-0203.
  21. Nag D, Chattopadhyay D, Maity CR. Superoxide dismutase and glutathione peroxidase in the pathogenesis of Mycobacterium tuberculosis and the effect of zinc supplementation. Ind Med Gaz 2009;CXLIII(1):1–6.
  22. Chattopadhyay DK, Maity CR, Nag D. Serum cholinesterase in patients suffering from tuberculosis and the effect of zinc supplementation. Ind Med Gaz 2007;CXLI(5):196–198.
  23. Chattopadhyay DK, Maity CR, Nag D. Level of glutamine synthetase in the serum of tubercular patients and the effect of zinc supplementation. Ind Med Gaz 2008;CXLII(3):81–84.
  24. Gazaryan IG, Krasnikow BF, Ashby GA, et al. Zinc is a potent inhibitor of thiol oxidoreductase activity and stimulates reactive oxygen species production by lipoamide dehydrogenase. J Bio Chem 2002;277(12):10064–10072. DOI: 10.1074/jbc.M108264200.
  25. Chattopadhyay DK, Maity CR, Nag D. Serum level of mycospecific immunoglobulins in different durations of anti-TB drug treatment in tubercular subjects. Ind Med Gaz 2007;CXLI(7):289–292.
  26. Chattopadhyay DK, Maity CR, Nag D. Effect of zinc supplementation on mycospecific immunoglobulins in tubercular patients. J Indian Med Assoc 2010;108(2):92–93. PMID: 20839565.
  27. Woolfolk CA, Shapiro B, Stadtman ER. Regulation of glutamine synthetase. I: purification and properties of glutamine synthetase from Escherichia coli. Arch Biochem Biophys 1966;116(1):177–192. DOI: 10.1016/0003-9861(66)90026-9.
  28. Wooliams JA, Weiner G, Anderson PH, et al. Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep. Res Vet Sci 1983;34(3):253–256. PMID: 6878874.
  29. Hestrin S. Estimation of acetylcholinesterase. J Biol Chem 1949;180:249–261.
  30. Ryndak MB, Wang S, Smith I, et al. The Mycobacterium tuberculosis high-affinity iron importer, Irt A, contains an FAD-binding domain. J Bacteriol 2010;192(3):861–869. DOI: 10.1128/JB.00223-09.
  31. Heym B, Zhang Y, Poulet S, et al. Characterization of the Kat G gene encoding a catalase peroxidase required for the isoniazid susceptibility of Mycobacterium tuberculosis. J Bacteriol 1993;175(13):4255–4259. DOI: 10.1128/jb.175.13.4255-4259.1993.
  32. Serafini A, Pisu D, Palu G, et al. The ESZ-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis. PLoS One 2013;8(10):e78351. DOI: 10.1371/journal.pone.0078351.
  33. Moayeri M, Leppla SH, Vrentas C, et al. Anthrax pathogenesis. Annu Rev Microbiol 2015;69:185–208. DOI: 10.1146/annurev-micro-091014-104523.
  34. Bonaventura P, Benedetti G, Albarede F, et al. Zinc and its role in immunity and inflammation. Autoimmun Rev 2015;14(4):277–285. DOI: 10.1016/j.autrev.2014.11.008.
  35. Chattopadhyay DK, Nag D. Efficacy of zinc supplementation as an adjunct to anti-tubercular drug therapy. Ind Med Gaz 2014;CXLVIII(1):21–24.
  36. Chattopadhyay DK, Maity CR, Nag D. Level of zinc in the serum of tubercular patients and the effect of zinc supplementation. Ind Med Gaz 2007;CXLI(1):7–10.
  37. Ruttkay-Nedecky B, Nejdl L, Gumulec J, et al. The role of metallothionein in oxidative stress. Int J Mol Sci 2013;14(3):6044–6066. DOI: 10.3390/ijms14036044.
  38. Harth G, Maslesa-Galic S, Tullius MV, et al. All four Mycobacterium tuberculosis gln A genes encode glutamine synthetase activities but only Gln A1 is abundantly expressed and essential for bacterial homeostasis. Mol Microbiol 2005;58(4):1157–1172. DOI: 10.1111/j.1365-2958.2005.04899.x.
  39. Tumani H, Shen G, Peter JB, et al. Glutamine synthetase in cerebrospinal fluid, serum and brain. Arch Neurol 1999;56:1241–1246. DOI: 10.1001/archneur.56.10.1241.
  40. Liaw SH, Kuo I, Eisenberg D. Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site. Protein Sci 1995;4(11):2358–2365. DOI: 10.1002/pro.5560041114.
  41. Bouron A, Oberwinkler J. Contribution of calcium-conducting channels to the transport of zinc ions. Pflugers Arch 2014;466(3): 381–387. DOI: 10.1007/s00424-013-1295-z.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.