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Fenton Reaction in vivo and in vitro. Possibilities and Limitations

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Abstract

The review considers the problem of hydrogen peroxide decomposition and hydroxyl radical formation in the presence of iron in vivo and in vitro. Analysis of the literature data allows us to conclude that, under physiological conditions, transport of iron, carried out with the help of carrier proteins, minimizes the possibility of appearance of free iron ions in cytoplasm of the cell. Under pathological conditions, when the process of transferring an iron ion from a donor protein to an acceptor protein can be disrupted due to modifications of the carrier proteins, iron ions can enter cytosol. However, at pH values close to neutral, which is typical for cytosol, iron ions are converted into water-insoluble hydroxides. This makes it impossible to decompose hydrogen peroxide according to the mechanism of the classical Fenton reaction. A similar situation is observed in vitro, since buffers with pH close to neutral are used to simulate free radical oxidation. At the same time, iron hydroxides are able to catalyze decomposition of hydrogen peroxide with formation of a hydroxyl radical. Decomposition of hydrogen peroxide with iron hydroxides is called Fenton-like reaction. Studying the features of Fenton-like reaction in biological systems is the subject of future research.

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Abbreviations

DMT1:

divalent metal transporter 1

FPN1:

ferroportin 1

HMOX1:

heme oxygenase 1

HP:

hephaestin

HRG1:

transmembrane heme-responsive gene 1

NTBI:

non-transferrin-bound iron

PCBP:

poly(rC)-binding protein (metallochaperone)

TF:

transferrin

TFR1:

transferrin receptor 1

References

  1. Fenton, H. J. H. (1894) LXXIII-oxidation of tartaric acid in presence of iron, J. Chem. Soc. Trans., 65, 899-910, https://doi.org/10.1039/CT8946500899.

    Article  CAS  Google Scholar 

  2. Dakin, H. D. (1922) Oxidations and Reductions in the Animal Body, Longmans Green and Co, London.

  3. Tarr, H. L. A. (1948) Control of rancidity in fish flesh: II. Physical and chemical methods, J. Fish. Res. Board Can., 7b, 237-247, https://doi.org/10.1139/f47-025.

    Article  Google Scholar 

  4. Zamenhof, S., Griboff, G., and Marullo, N. (1954) Studies on the resistance of desoxyribonucleic acids to physical and chemical factors, Biochim. Biophys. Acta, 13, 459-470, https://doi.org/10.1016/0006-3002(54)90362-5.

    Article  CAS  PubMed  Google Scholar 

  5. Haber, F., and Weiss, J. (1934) The catalytic decomposition of hydrogen peroxide by iron salts, Proc. R. Soc. Lond. Ser. A Math. Phys. Sci., 147, 332-351, https://doi.org/10.1098/rspa.1934.0221.

    Article  CAS  ADS  Google Scholar 

  6. Knutson, M., and Wessling-Resnick, M. (2003) Iron metabolism in the reticuloendothelial system, Crit. Rev. Biochem. Mol. Biol., 38, 61-88, https://doi.org/10.1080/713609210.

    Article  CAS  PubMed  Google Scholar 

  7. Knutson, M. D. (2017) Iron transport proteins: gateways of cellular and systemic iron homeostasis, J. Biol. Chem., 292, 12735-12743, https://doi.org/10.1074/jbc.R117.786632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tenhunen, R., Grasbeck, R., Kouvonen, I., and Lundberg, M. (1980) An intestinal receptor for heme: its partial characterization, Int. J. Biochem., 12, 713-716, https://doi.org/10.1016/0020-711X(80)90149-4.

    Article  CAS  PubMed  Google Scholar 

  9. Grasbeck, R., Kouvonen, I., Lundberg, M., and Tenhunen, R. (2009) An intestinal receptor for heme, Scand. J. Haematol., 23, 5-9, https://doi.org/10.1111/j.1600-0609.1979.tb02845.x.

    Article  Google Scholar 

  10. White, C., Yuan, X., Schmidt, P. J., Bresciani, E., Samuel, T. K., Campagna, D., Hall, C., Bishop, K., Calicchio, M. L., Lapierre, A., Ward, D. M., Liu, P., Fleming, M. D., and Hamza, I. (2013) HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis, Cell Metab., 17, 261-270, https://doi.org/10.1016/j.cmet.2013.01.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rajagopal, A., Rao, A. U., Amigo, J., Tian, M., Upadhyay, S. K., Hall, C., Uhm, S., Mathew, M. K., Fleming, M. D., Paw, B. H., Krause, M., and Hamza, I. (2008) Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins, Nature, 453, 1127-1131, https://doi.org/10.1038/nature06934.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  12. Weintraub, L. R., Weinstein, M. B., Huser, H. J., and Rafal, S. (1968) Absorption of hemoglobin iron: the role of a heme-splitting substance in the intestinal mucosa, J. Clin. Invest., 47, 531-539, https://doi.org/10.1172/JCI105749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., and Hediger, M. A. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter, Nature, 388, 482-488, https://doi.org/10.1038/41343.

    Article  CAS  PubMed  ADS  Google Scholar 

  14. Fleming, M. D., Trenor, C. C., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F., and Andrews, N. C. (1997) Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene, Nat. Genetics, 16, 383-386, https://doi.org/10.1038/ng0897-383.

    Article  CAS  PubMed  Google Scholar 

  15. Gunshin, H., Fujiwara, Y., Custodio, A. O., DiRenzo, C., Robine, S., and Andrews, N. C. (2005) Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver, J. Clin. Invest., 115, 1258-1266, https://doi.org/10.1172/JCI24356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shawki, A., Anthony, S. R., Nose, Y., Engevik, M. A., Niespodzany, E. J., Barrientos, T., Öhrvik, H., Worrell, R. T., Thiele, D. J., and Mackenzie, B. (2015) Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese, Am. J. Physiol. Gastrointest. Liver. Physiol., 309, G635-G647, https://doi.org/10.1152/ajpgi.00160.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. McKie, A. T., Barrow, D., Latunde-Dada, G. O., Rolfs, A., Sager, G., Mudaly, E., Mudaly, M., Richardson, C., Barlow, D., Bomford, A., Peters, T. J., Raja, K. B., Shirali, S., Hediger, M. A., Farzaneh, F., and Simpson, R. J. (2001) An iron-regulated ferric reductase associated with the absorption of dietary iron, Science, 291, 1755-1759, https://doi.org/10.1126/science.1057206.

    Article  CAS  PubMed  ADS  Google Scholar 

  18. Shawki, A., Engevik, M. A., Kim, R. S., Knight, P. B., Baik, R. A., Anthony, S. R., Worrell, R. T., Shull, G. E., and Mackenzie, B. (2016) Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse, Am. J. Physiol. Gastrointest. Liver. Physiol., 311, G423-G430, https://doi.org/10.1152/ajpgi.00167.2016.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Illing, A. C., Shawki, A., Cunningham, C. L., and Mackenzie, B. (2012) Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1, J. Biol. Chem., 287, 30485-30496, https://doi.org/10.1074/JBC.M112.364208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Abboud, S., and Haile, D. J. (2000) A novel mammalian iron-regulated protein involved in intracellular iron metabolism, J. Biol. Chem., 275, 19906-19912, https://doi.org/10.1074/jbc.M000713200.

    Article  CAS  PubMed  Google Scholar 

  21. Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palls, J., Fleming, M. D., Andrews, N. C., and Leonard, I. (2000) Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter, Nature, 403, 776-781, https://doi.org/10.1038/35001596.

    Article  CAS  PubMed  ADS  Google Scholar 

  22. McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., and Simpson, R. J. (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation, Mol. Cell, 5, 299-309, https://doi.org/10.1016/S1097-2765(00)80425-6.

    Article  CAS  PubMed  Google Scholar 

  23. Mitchell, C. J., Shawki, A., Ganz, T., Nemeth, E., and Mackenzie, B. (2014) Functional properties of human ferroportin, a cellular iron exporter reactive also with cobalt and zinc, Am. J. Physiol. Cell Physiol., 306, C450-C459, https://doi.org/10.1152/ajpcell.00348.2013.

    Article  CAS  PubMed  Google Scholar 

  24. Fuqua, B. K., Lu, Y., Darshan, D., Frazer, D. M., Wilkins, S. J., Wolkow, N., Bell, A. G., Hsu, J., Yu, C. C., Chen, H., Dunaief, J. L., Anderson, G. J., and Vulpe, C. D. (2014) The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice, PLoS One, 9, e98792, https://doi.org/10.1371/journal.pone.0098792.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  25. Yanatori, I., Yasui, Y., Tabuchi, M., and Kishi, F. (2014) Chaperone protein involved in transmembrane transport of iron, Biochem. J., 462, 25-37, https://doi.org/10.1042/BJ20140225.

    Article  CAS  PubMed  Google Scholar 

  26. Leidgens, S., Bullough, K. Z., Shi, H., Li, F., Shakoury-Elizeh, M., Yabe, T., Subramanian, P., Hsu, E., Natarajan, N., Nandal, A., Stemmler, T. L., and Philpott, C. C. (2013) Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin, J. Biol. Chem., 288, 17791-17802, https://doi.org/10.1074/jbc.M113.460253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cozzi, A., Corsi, B., Levi, S., Santambrogio, P., Albertini, A., and Arosio, P. (2000) Overexpression of wild type and mutated human ferritin H-chain in HeLa cells: in vivo role of ferritin ferroxidase activity, J. Biol. Chem., 275, 25122-25129, https://doi.org/10.1074/jbc.M003797200.

    Article  CAS  PubMed  Google Scholar 

  28. Santambrogio, P., Levi, S., Cozzi, A., Corsi, B., and Arosio, P. (1996) Evidence that the specificity of iron incorporation into homopolymers of human ferritin L- and H-chains is conferred by the nucleation and ferroxidase centres, Biochem. J., 314, 139-144, https://doi.org/10.1042/bj3140139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Svobodova, H., Kosnáč, D., Tanila, H., Wagner, A., Trnka, M., Vitovič, P., Hlinkova, J., Vavrinsky, E., Ehrlich, H., Polák, Š., and Kopani, M. (2020) Iron-oxide minerals in the human tissues, BioMetals, 33, 1-13, https://doi.org/10.1007/s10534-020-00232-6.

    Article  CAS  PubMed  Google Scholar 

  30. Andrews, N. C. (2010) Ferrit(in)ing out new mechanisms in iron homeostasis, Cell Metab., 12, 203-204, https://doi.org/10.1016/j.cmet.2010.08.011.

    Article  CAS  PubMed  Google Scholar 

  31. Vanoaica, L., Darshan, D., Richman, L., Schumann, K., and Kuhn, L. C. (2010) Intestinal ferritin H is required for an accurate control of iron absorption, Cell Metab., 12, 273-282, https://doi.org/10.1016/j.cmet.2010.08.003.

    Article  CAS  PubMed  Google Scholar 

  32. Darwich, A. S., Aslam, U., Ashcroft, D. M., and Rostami-Hodjegan, A. (2014) Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans, Drug Metab. Disp., 42, 2016-2022, https://doi.org/10.1124/dmd.114.058404.

    Article  CAS  Google Scholar 

  33. Kidane, T. Z., Sauble, E., and Linder, M. C. (2006) Release of iron from ferritin requires lysosomal activity, Am. J. Physiol. Cell Physiol., 291, C445-C455, https://doi.org/10.1152/ajpcell.00505.2005.

    Article  CAS  PubMed  Google Scholar 

  34. Gryzik, M., Srivastava, A., Longhi, G., Bertuzzi, M., Gianoncelli, A., Carmona, F., Poli, M., and Arosio, P. (2017) Expression and characterization of the ferritin binding domain of nuclear receptor coactivator-4 (NCOA4), Biochim. Biophys. Acta General Subjects, 1861, 2710-2716, https://doi.org/10.1016/j.bbagen.2017.07.015.

    Article  CAS  PubMed  Google Scholar 

  35. Mancias, J. D., Wang, X., Gygi, S. P., Harper, J. W., and Kimmelman, A. C. (2014) Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy, Nature, 508, 105-109, https://doi.org/10.1038/nature13148.

    Article  CAS  ADS  Google Scholar 

  36. Shi, H., Bencze, K. Z., Stemmler, T. L., and Philpott, C. C. (2008) A cytosolic iron chaperone that delivers iron to ferritin, Science, 320, 1207-1210, https://doi.org/10.1126/science.1157643.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  37. Lane, D. J., and Richardson, D. R. (2014) Chaperone turns gatekeeper: PCBP2 and DMT1 form an iron-transport pipeline, Biochem. J., 462, e1-e3, https://doi.org/10.1042/BJ20140720.

    Article  CAS  PubMed  Google Scholar 

  38. Yanatori, I., Richardson, D. R., Imada, K., and Kishi, F. (2016) Iron export through the transporter ferroportin 1 is modulated by the iron chaperone PCBP2, J. Biol. Chem., 291, 17303-17318, https://doi.org/10.1074/jbc.M116.721936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Han, O., and Kim, E. Y. (2007) Colocalization of ferroportin-1 with hephaestin on the basolateral membrane of human intestinal absorptive cells, J. Cell. Biochem., 101, 1000-1010, https://doi.org/10.1002/jcb.21392.

    Article  CAS  PubMed  Google Scholar 

  40. Yeh, K. Y., Yeh, M., and Glass, J. (2011) Interactions between ferroportin and hephaestin in rat enterocytes are reduced after iron ingestion, Gastroenterology, 141, 292-299, https://doi.org/10.1053/j.gastro.2011.03.059.

    Article  CAS  PubMed  Google Scholar 

  41. Harris, W. R. (1986) Estimation of the ferrous-transferrin binding constants based on thermodynamic studies of nickel(II)transferrin, J. Inorg. Biochem., 27, 41-52, https://doi.org/10.1016/0162-0134(86)80107-6.

    Article  CAS  PubMed  Google Scholar 

  42. Terpstra, T., McNally, J., Han, T. H. L., Ha-Duong, N. T., El-Hage-Chahine, J. M., and Bou-Abdallah, F. (2014) Direct thermodynamic and kinetic measurements of Fe2+ and Zn2+ binding to human serum transferrin, J. Inorg. Biochem., 136, 24-32, https://doi.org/10.1016/J.JINORGBIO.2014.03.007.

    Article  CAS  PubMed  Google Scholar 

  43. Bou Abdallah, F., and El Hage Chahine, J. M. H. (1998) Transferrins. Hen ovo-transferrin, interaction with bicarbonate and iron uptake, Eur. J. Biochem., 258, 1022-1031, https://doi.org/10.1046/J.1432-1327.1998.2581022.X.

    Article  CAS  PubMed  Google Scholar 

  44. Wally, J., and Buchanan, S. K. (2007) A structural comparison of human serum transferrin and human lactoferrin, BioMetals, 20, 249-262, https://doi.org/10.1007/s10534-006-9062-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dautry Varsat, A., Ciechanover, A., and Lodish, H. F. (1983) pH and the recycling of transferrin during receptor-mediated endocytosis, Proc. Natl. Acad. Sci. USA, 80, 2258-2262, https://doi.org/10.1073/pnas.80.8.2258.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  46. Nunez, M. T., Gaete, V., Watkins, J. A., and Glass, J. (1990) Mobilization of iron from endocytic vesicles. The effects of acidification and reduction, J. Biol. Chem., 265, 6688-6692, https://doi.org/10.1016/s0021-9258(19)39205-1.

    Article  CAS  PubMed  Google Scholar 

  47. El Hage Chahine, J. M., Hemadi, M., and Ha-Duong, N. T. (2012) Uptake and release of metal ions by transferrin and interaction with receptor 1, Biochim. Biophys. Acta General Subjects, 1820, 334-347, https://doi.org/10.1016/j.bbagen.2011.07.008.

    Article  CAS  Google Scholar 

  48. Abbaspour, N., Hurrell, R., and Kelishadi, R. (2014) Review on iron and its importance for human health, J. Res. Med. Sci., 19, 164-174.

    PubMed  PubMed Central  Google Scholar 

  49. Gottlieb, Y., Truman, M., Cohen, L. A., Leichtmann-Bardoogo, Y., and Meyron-Holtz, E. G. (2012) Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol, Haematologica, 97, 1489-1493, https://doi.org/10.3324/haematol.2012.063651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Korolnek, T., and Hamza, I. (2015) Macrophages and iron trafficking at the birth and death of red cells, Blood, 125, 2893-2897, https://doi.org/10.1182/blood-2014-12-567776.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Garby, L., and Noyes, W. D. (1959) Studies on hemoglobin metabolism. II. Pathways of hemoglobin iron metabolism in normal man, J. Clin. Invest., 38, 1484-1486, https://doi.org/10.1172/JCI103926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kristiansen, M., Graversen, J. H., Jacobsen, C., Sonne, O., Hoffman, H. J., Law, S. K. A., and Moestrup, S. K. (2001) Identification of the haemoglobin scavenger receptor, Nature, 409, 198-201, https://doi.org/10.1038/35051594.

    Article  CAS  PubMed  ADS  Google Scholar 

  53. Schaer, C. A., Schoedon, G., Imhof, A., Kurrer, M. O., and Schaer, D. J. (2006) Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin, Circ. Res., 99, 943-950, https://doi.org/10.1161/01.RES.0000247067.34173.1b.

    Article  CAS  PubMed  Google Scholar 

  54. Schaer, D. J., Schaer, C. A., Buehler, P. W., Boykins, R. A., Schoedon, G., Alayash, A. I., and Schaffner, A. (2006) CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin, Blood, 107, 373-380, https://doi.org/10.1182/blood-2005-03-1014.

    Article  CAS  PubMed  Google Scholar 

  55. Hvidberg, V., Maniecki, M. B., Jacobsen, C., Højrup, P., Møller, H. J., and Moestrup, S. K. (2005) Identification of the receptor scavenging hemopexin-heme complexes, Blood, 106, 2572-2579, https://doi.org/10.1182/blood-2005-03-1185.

    Article  CAS  PubMed  Google Scholar 

  56. Vinchi, F., Gastaldi, S., Silengo, L., Altruda, F., and Tolosano, E. (2008) Hemopexin prevents endothelial damage and liver congestion in a mouse model of heme overload, Am. J. Pathol., 173, 289-299, https://doi.org/10.2353/ajpath.2008.071130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Morgan, E. H., Smith, G. D., and Peters, T. J. (1986) Uptake and subcellular processing of 59Fe-125I-labelled transferrin by rat liver, Biochem. J., 237, 163-173, https://doi.org/10.1042/bj2370163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wang, C. Y., and Knutson, M. D. (2013) Hepatocyte divalent metal-ion transporter-1 is dispensable for hepatic iron accumulation and non-transferrin-bound iron uptake in mice, Hepatology, 58, 788-798, https://doi.org/10.1002/hep.26401.

    Article  CAS  PubMed  Google Scholar 

  59. Nam, H., Wang, C. Y., Zhang, L., Zhang, W., Hojyo, S., Fukada, T., and Knutson, M. D. (2013) ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: Implications for tissue iron uptake in iron-related disorders, Haematologica, 98, 1049-1057, https://doi.org/10.3324/haematol.2012.072314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Grootveld, M., Bell, J. D., Halliwell, B., Aruoma, O. I., Bomford, A., and Sadler, P. J. (1989) Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis, J. Biol. Chem., 264, 4417-4422, https://doi.org/10.1016/S0021-9258(18)83758-9.

    Article  CAS  PubMed  Google Scholar 

  61. Randell, E. W., Parkes, J. G., Olivieri, N. F., and Templeton, D. M. (1994) Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron, J. Biol. Chem., 269, 16046-16053, https://doi.org/10.1016/s0021-9258(17)33971-6.

    Article  CAS  PubMed  Google Scholar 

  62. Singh, A., Kong, Q., Luo, X., Petersen, R. B., Meyerson, H., and Singh, N. (2009) Prion protein (PrP) knock-out mice show altered iron metabolism: a functional role for PrP in iron uptake and transport, PLoS One, 4, e6115, https://doi.org/10.1371/journal.pone.0006115.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  63. Shawki, A., Knight, P. B., Maliken, B. D., Niespodzany, E. J., and Mackenzie, B. (2012) H+-coupled divalent metal-ion transporter-1: functional properties, physiological roles and therapeutics, Curr. Top. Membr., 70, 169-214, https://doi.org/10.1016/B978-0-12-394316-3.00005-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mackenzie, B., Takanaga, H., Hubert, N., Rolfs, A., and Hediger, M. A. (2007) Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1), Biochem. J., 403, 59-69, https://doi.org/10.1042/BJ20061290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yanatori, I., Richardson, D. R., Toyokuni, S., and Kishi, F. (2020) The new role of poly (rC)-binding proteins as iron transport chaperones: proteins that could couple with inter-organelle interactions to safely traffic iron, Biochim. Biophys. Acta General Subjects, 1864, 129685, https://doi.org/10.1016/j.bbagen.2020.129685.

    Article  CAS  PubMed  Google Scholar 

  66. Ghanem, L. R., Kromer, A., Silverman, I. M., Chatterji, P., Traxler, E., Penzo-Mendez, A., Weiss, M. J., Stanger, B. Z., and Liebhaber, S. A. (2016) The Poly(C) binding protein Pcbp2 and its retrotransposed derivative Pcbp1 are independently essential to mouse development, Mol. Cell. Biol., 36, 304-319, https://doi.org/10.1128/mcb.00936-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Yanatori, I., and Kishi, F. (2019) DMT1 and iron transport, Free Radic Biol. Med., 133, 55-63, https://doi.org/10.1016/j.freeradbiomed.2018.07.020.

    Article  CAS  PubMed  Google Scholar 

  68. Yanatori, I., Richardson, D. R., Toyokuni, S., and Kishi, F. (2019) How iron is handled in the course of heme catabolism: integration of heme oxygenase with intracellular iron transport mechanisms mediated by poly (rC)-binding protein-2, Arch. Biochem. Biophys., 672, 108071, https://doi.org/10.1016/j.abb.2019.108071.

    Article  CAS  PubMed  Google Scholar 

  69. Yanatori, I., Richardson, D. R., Toyokuni, S., and Kishi, F. (2017) The iron chaperone poly(rC)-binding protein 2 forms a metabolon with the heme oxygenase 1/cytochrome P450 reductase complex for heme catabolism and iron transfer, J. Biol. Chem., 292, 13205-13229, https://doi.org/10.1074/jbc.M117.776021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jacobs, A. (1977) Low molecular weight intracellular iron transport compounds, Blood, 50, 433-439, https://doi.org/10.1182/blood.v50.3.433.433.

    Article  CAS  PubMed  Google Scholar 

  71. Philpott, C. C., Ryu, M. S., Frey, A., and Patel, S. (2017) Cytosolic iron chaperones: proteins delivering iron cofactors in the cytosol of mammalian cells, J. Biol. Chem., 292, 12764-12771, https://doi.org/10.1074/jbc.R117.791962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Petrak, J., and Vyoral, D. (2005) Hephaestin – a ferroxidase of cellular iron export, Int. J. Biochem. Cell. Biol., 37, 1173-1178, https://doi.org/10.1016/j.biocel.2004.12.007.

    Article  CAS  PubMed  Google Scholar 

  73. Lutsenko, S., Barnes, N. L., Bartee, M. Y., and Dmitriev, O. Y. (2007) Function and regulation of human copper-transporting ATPases, Physiol. Rev., 87, 1011-1046, https://doi.org/10.1152/physrev.00004.2006.

    Article  CAS  PubMed  Google Scholar 

  74. Schulz, K., Vulpe, C. D., Harris, L. Z., and David, S. (2011) Iron efflux from oligodendrocytes is differentially regulated in gray and white matter, J. Neurosci., 31, 13301-13311, https://doi.org/10.1523/JNEUROSCI.2838-11.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yeh, K., Yeh, M., Mims, L., and Glass, J. (2009) Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium, Am. J. Physiol. Gastr. Liv. Physiol., 296, G55-G65, https://doi.org/10.1152/ajpgi.90298.2008.

    Article  CAS  Google Scholar 

  76. Coffey, R., and Ganz, T. (2017) Iron homeostasis: an anthropocentric perspective, J. Biol. Chem., 292, 12727-12734, https://doi.org/10.1074/jbc.R117.781823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Drakesmith, H., Nemeth, E., and Ganz, T. (2015) Ironing out ferroportin, Cell Metab., 22, 777-787, https://doi.org/10.1016/j.cmet.2015.09.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sudarev, V. V., Dolotova, S. M., Bukhalovich, S. M., Bazhenov, S. V., Ryzhykau, Y. L., Uversky, V. N., Bondarev, N. A., Osipov, S. D., Mikhailov, A. E., Kuklina, D. D., Murugova, T. N., Manukhov, I. V., Rogachev, A. V., Gordeliy, V. I., Gushchin, I. Y., Kuklin, A. I., and Vlasov, A. V. (2023) Ferritin self-assembly, structure, function, and biotechnological applications, Int. J. Biol. Macromol., 224, 319-343, https://doi.org/10.1016/j.ijbiomac.2022.10.126.

    Article  CAS  PubMed  Google Scholar 

  79. Arosio, P., Carmona, F., Gozzelino, R., Maccarinelli, F., and Poli, M. (2015) The importance of eukaryotic ferritins in iron handling and cytoprotection, Biochem. J., 472, 1-15, https://doi.org/10.1042/BJ20150787.

    Article  CAS  PubMed  Google Scholar 

  80. Ebrahimi, K. H., Hagedoorn, P. L., and Hagen, W. R. (2015) Self-assembly is prerequisite for catalysis of Fe(II) oxidation by catalytically active subunits of ferritin, J. Biol. Chem., 290, 26801-26810, https://doi.org/10.1074/jbc.M115.678375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chen, P., De Meulenaere, E., Deheyn, D. D., and Bandaru, P. R. (2020) Iron redox pathway revealed in ferritin via electron transfer analysis, Sci. Rep., 10, 4033, https://doi.org/10.1038/s41598-020-60640-z.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  82. Laghaei, R., Evans, D. G., and Coalson, R. D. (2013) Metal binding sites of human H-chain ferritin and iron transport mechanism to the ferroxidase sites: a molecular dynamics simulation study, Prot. Struct. Func. Bioinf., 81, 1042-1050, https://doi.org/10.1002/prot.24251.

    Article  CAS  Google Scholar 

  83. Bou-Abdallah, F., Zhao, G., Biasiotto, G., Poli, M., Arosio, P., and Chasteen, N. D. (2008) Facilitated diffusion of iron(II) and dioxygen substrates into human H-chain ferritin. A fluorescence and absorbance study employing the ferroxidase center substitution Y34W, J. Am. Chem. Soc., 130, 17801-17811, https://doi.org/10.1021/ja8054035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Bou-Abdallah, F. (2010) The iron redox and hydrolysis chemistry of the ferritins, Biochim. Biophys. Acta, 1800, 719-731, https://doi.org/10.1016/j.bbagen.2010.03.021.

    Article  CAS  PubMed  Google Scholar 

  85. Winterbourn, C. C. (1995) Toxicity of iron and hydrogen peroxide: the Fenton reaction, Toxicol. Lett., 82-83, 969-974, https://doi.org/10.1016/0378-4274(95)03532-X.

    Article  CAS  PubMed  Google Scholar 

  86. López-Castro, J. D., Delgado, J. J., Perez-Omil, J. A., Gálvez, N., Cuesta, R., Watt, R. K., and Domínguez-Vera, J. M. (2012) A new approach to the ferritin iron core growth: influence of the H/L ratio on the core shape, Dalton Transactions, 41, 1320-1324, https://doi.org/10.1039/c1dt11205h.

    Article  CAS  PubMed  Google Scholar 

  87. Luzzago, A., Arosio, P., Iacobello, C., Ruggeri, G., Capucci, L., Brocchi, E., De Simone, F., Gamba, D., Gabri, E., Levi, S., and Albertini, A. (1986) Immunochemical characterization of human liver and heart ferritins with monoclonal antibodies, Biochim. Biophys. Acta Protein Struct. Mol., 872, 61-71, https://doi.org/10.1016/0167-4838(86)90147-0.

    Article  CAS  Google Scholar 

  88. Sala, D., Ciambellotti, S., Giachetti, A., Turano, P., and Rosato, A. (2017) Investigation of the iron(II) release mechanism of human H-ferritin as a function of pH, J. Chem. Inform. Model., 57, 2112-2118, https://doi.org/10.1021/acs.jcim.7b00306.

    Article  CAS  Google Scholar 

  89. Rousseau, I., and Puntarulo, S. (2009) Ferritin-dependent radical generation in rat liver homogenates, Toxicology, 264, 155-161, https://doi.org/10.1016/j.tox.2009.07.019.

    Article  CAS  PubMed  Google Scholar 

  90. Melman, G., Bou-Abdallah, F., Vane, E., Maura, P., Arosio, P., and Melman, A. (2013) Iron release from ferritin by flavin nucleotides, Biochim. Biophys. Acta General Subjects, 1830, 4669-4674, https://doi.org/10.1016/j.bbagen.2013.05.031.

    Article  CAS  Google Scholar 

  91. Bou-Abdallah, F., Paliakkara, J., Melman, G., and Melman, A. (2018) Reductive mobilization of iron from intact ferritin: mechanisms and physiological implication, Pharmaceuticals, 11, 120, https://doi.org/10.3390/ph11040120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Koochana, P. K., Mohanty, A., Parida, A., Behera, N., Behera, P. M., Dixit, A., and Behera, R. K. (2021) Flavin-mediated reductive iron mobilization from frog M and Mycobacterial ferritins: impact of their size, charge and reactivities with NADH/O2, J. Biol. Inorg. Chem., 26, 265-281, https://doi.org/10.1007/s00775-021-01850-2.

    Article  CAS  PubMed  Google Scholar 

  93. Koochana, P. K., Mohanty, A., Das, S., Subhadarshanee, B., Satpati, S., Dixit, A., Sabat, S. C., and Behera, R. K. (2018) Releasing iron from ferritin protein nanocage by reductive method: the role of electron transfer mediator, Biochim. Biophys. Acta General Subjects, 1862, 1190-1198, https://doi.org/10.1016/j.bbagen.2018.02.011.

    Article  CAS  PubMed  Google Scholar 

  94. Tosha, T., Behera, R. K., Ng, H. L., Bhattasali, O., Alber, T., and Theil, E. C. (2012) Ferritin protein nanocage ion channels, J. Biol. Chem., 287, 13016-13025, https://doi.org/10.1074/jbc.M111.332734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Liu, X., Jin, W., and Theil, E. C. (2003) Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral, Proc. Natl. Acad. Sci. USA, 100, 3653-3658, https://doi.org/10.1073/pnas.0636928100.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  96. Assia, N., Goldenberg-Cohen, N., Rechavi, G., Amariglio, N., and Cohen, Y. (2010) Mutation analysis of the ferritin L-chain gene in age-related cataract, Mol. Vis., 16, 2487-2493.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Yang, Y., Lin, T., Kuang, P., and Chen, X. (2021) Ferritin L-subunit gene mutation and hereditary hyperferritinaemia cataract syndrome (HHCS): a case report and literature review, Hematology, 26, 896-903, https://doi.org/10.1080/16078454.2021.1995111.

    Article  PubMed  Google Scholar 

  98. Bossoni, L., Grand Moursel, L., Bulk, M., Simon, B. G., Webb, A., Van Der Weerd, L., Huber, M., Carretta, P., Lascialfari, A., and Oosterkamp, T. H. (2017) Human-brain ferritin studied by muon spin rotation: a pilot study, J. Phys. Condens. Mat., 29, 415801, https://doi.org/10.1088/1361-648X/aa80b3.

    Article  Google Scholar 

  99. Strbak, O., Balejcikova, L., Kmetova, M., Gombos, J., Trancikova, A., Pokusa, M., and Kopcansky, P. (2020) Quantification of iron release from native ferritin and magnetoferritin induced by vitamins B2 and C, Int. J. Mol. Sci., 21, 6332, https://doi.org/10.3390/ijms21176332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kirschvink, J. L., Kobayashi-Kirschvink, A., and Woodford, B. J. (1992) Magnetite biomineralization in the human brain, Proc. Natl. Acad. Sci. USA, 89, 7683-7687, https://doi.org/10.1073/pnas.89.16.7683.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  101. Wessling-Resnick, M. (2010) Iron homeostasis and the inflammatory response, Annu. Rev. Nutr., 30, 105-122, https://doi.org/10.1146/annurev.nutr.012809.104804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Hagemeier, J., Geurts, J. J. G., and Zivadinov, R. (2012) Brain iron accumulation in aging and neurodegenerative disorders, Exp. Rev. Neurother., 12, 1467-1480, https://doi.org/10.1586/ern.12.128.

    Article  CAS  Google Scholar 

  103. Frank-Cannon, T. C., Alto, L. T., McAlpine, F. E., and Tansey, M. G. (2009) Does neuroinflammation fan the flame in neurodegenerative diseases? Mol. Neurodegener., 4, 47, https://doi.org/10.1186/1750-1326-4-47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Jung, M., Mertens, C., Tomat, E., and Brüne, B. (2019) Iron as a central player and promising target in cancer progression, Int. J. Mol. Sci., 20, 273, https://doi.org/10.3390/ijms20020273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Milic, S., Mikolasevic, I., Orlic, L., Devcic, E., Starcevic-Cizmarevic, N., Stimac, D., Kapovic, M., and Ristic, S. (2016) The role of iron and iron overload in chronic liver disease, Med. Sci. Mon., 22, 2144-2151, https://doi.org/10.12659/MSM.896494.

    Article  CAS  Google Scholar 

  106. Kobayashi, M., Suhara, T., Baba, Y., Kawasaki, N. K., Higa, J. K., and Matsui, T. (2018) Pathological roles of iron in cardiovascular disease, Curr. Drug Target, 19, 1068-1076, https://doi.org/10.2174/1389450119666180605112235.

    Article  CAS  Google Scholar 

  107. Ganz, T. (2017) Does Pathological iron overload impair the function of human lungs? EBioMedicine, 20, 13-14, https://doi.org/10.1016/j.ebiom.2017.05.023.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Weiss, J. (1935) Electron transfer processes in the mechanism of oxidation and reduction reactions in solutions [in German], Naturwissenschaften, 23, 64-69, https://doi.org/10.1007/BF01497021.

    Article  CAS  ADS  Google Scholar 

  109. Stumm, W., and Lee, G. F. (1961) Oxygenation of ferrous iron, Indust. Engin. Chem., 53, 143-146, https://doi.org/10.1021/ie50614a030.

    Article  CAS  Google Scholar 

  110. Smythe, C. V. (1931) The mechanism of iron catalysis in certain oxidations, J. Biol. Chem., 90, 251-265, https://doi.org/10.1016/S0021-9258(18)76678-7.

    Article  CAS  Google Scholar 

  111. Yuan, Z., Zhang, G., Lin, J., Zeng, X., Ma, X., Wang, X., Wang, S., and Jia, Y. (2019) The stability of Fe(III)-As(V) co-precipitate in the presence of ascorbic acid: effect of pH and Fe/As molar ratio, Chemosphere, 218, 670-679, https://doi.org/10.1016/j.chemosphere.2018.11.142.

    Article  CAS  PubMed  ADS  Google Scholar 

  112. Khoshaman, K., Yousefi, R., Tamaddon, A. M., Saso, L., and Moosavi-Movahedi, A. A. (2015) The impact of Hydrogen peroxide on structure, stability and functional properties of Human R12C mutant alphaA-crystallin: the imperative insights into pathomechanism of the associated congenital cataract incidence, Free Radic. Biol. Med., 89, 819-830, https://doi.org/10.1016/j.freeradbiomed.2015.09.013.

    Article  CAS  PubMed  Google Scholar 

  113. Sreenivasan, S., and Rathore, A. S. (2023) Combined presence of ferrous ions and hydrogen peroxide in normal saline and in vitro models induces enhanced aggregation of therapeutic IgG due to hydroxyl radicals, Mol. Pharmac., 20, 3033-3048, https://doi.org/10.1021/acs.molpharmaceut.3c00051.

    Article  CAS  Google Scholar 

  114. Roginsky, V. A., Barsukova, T. K., Bruchelt, G., and Stegmann, H. B. (1997) Ion bound to ferritin catalyzes ascorbate oxidation: effects of chelating agents, Biochim. Biophys. Acta General Subjects, 1335, 33-39, https://doi.org/10.1016/S0304-4165(96)00120-1.

    Article  CAS  Google Scholar 

  115. Wang, K., and Spector, A. (1995) Alpha-crystallin can act as a chaperone under conditions of oxidative stress, Invest Ophthalmol. Vis. Sci., 36, 311-321.

    CAS  PubMed  Google Scholar 

  116. Fischbacher, A., Von, S. C., and Schmidt, T. C. (2017) Hydroxyl radical yields in the Fenton process under various pH, ligand concentrations and hydrogen peroxide/Fe(II) ratios, Chemosphere, 182, 738-744, https://doi.org/10.1016/j.chemosphere.2017.05.039.

    Article  CAS  PubMed  ADS  Google Scholar 

  117. Grundl, T., and Delwiche, J. (1993) Kinetics of ferric oxyhydroxide precipitation, J. Contamin. Hydrol., 14, 71-87, https://doi.org/10.1016/0169-7722(93)90042-Q.

    Article  CAS  ADS  Google Scholar 

  118. Murphy, P. J., Posner, A. M., and Quirk, J. P. (1976) Characterization of partially neutralized ferric nitrate solutions, J. Colloid Interfac. Sci., 56, 270-283, https://doi.org/10.1016/0021-9797(76)90253-8.

    Article  CAS  ADS  Google Scholar 

  119. Poliansky, N. B., Motyakin, M. V., Kasparov, V. V., Novikov, I. A., and Muranov, K. O. (2023) Oxidative damage to bL-crystallin in vitro by iron compounds formed in physiological buffers, Biophys. Chem., 294, 106963, https://doi.org/10.1016/j.bpc.2023.106963.

    Article  CAS  PubMed  Google Scholar 

  120. Lin, S. S., and Gurol, M. D. (1998) Catalytic decomposition of hydrogen peroxide on iron oxide: kinetics, mechanism, and implications, Free Radic. Res., 23, 593-614, https://doi.org/10.3109/10715769509065280.

    Article  Google Scholar 

  121. Lin, Z. R., Zhao, L., and Dong, Y. H. (2015) Quantitative characterization of hydroxyl radical generation in a goethite-catalyzed Fenton-like reaction, Chemosphere, 141, 7-12, https://doi.org/10.1016/j.chemosphere.2015.05.066.

    Article  CAS  PubMed  ADS  Google Scholar 

  122. Manevich, Y., Held, K. D., and Biaglow, J. E. (1997) Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation, Radiat. Res., 148, 580-591, https://doi.org/10.2307/3579734.

    Article  CAS  PubMed  ADS  Google Scholar 

  123. Josephy, P. D., Eling, T., and Mason, R. P. (1982) The horseradish peroxidase-catalyzed oxidation of 3,5,3′,5′-tetramethylbenzidine. Free radical and charge-transfer complex intermediates, J. Biol. Chem., 257, 3669-3675, https://doi.org/10.1016/S0021-9258(18)34832-4.

    Article  CAS  PubMed  Google Scholar 

  124. Matsumoto, T., Chang, H. C., Wakizaka, M., Ueno, S., Kobayashi, A., Nakayama, A., Taketsugu, T., and Kato, M. (2013) Nonprecious-metal-assisted photochemical hydrogen production from ortho-phenylenediamine, J. Am. Chem. Soc., 135, 8646-8654, https://doi.org/10.1021/ja4025116.

    Article  CAS  PubMed  Google Scholar 

  125. Davies, M. J. (2016) Detection and characterisation of radicals using electron paramagnetic resonance (EPR) spin trapping and related methods, Methods, 109, 21-30, https://doi.org/10.1016/j.ymeth.2016.05.013.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The author expresses his gratitude to Dr. L. M. Pisarenko (Institute of Chemical Physics, Russian Academy of sciences) for fruitful discussion of the problem of heterogenous catalysis with participation of iron hydroxide.

Funding

This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation in the framework of the project 0084-2014-0014, State registration no. 01201253314.

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Correspondence to Konstantin O. Muranov.

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Translated from Uspekhi Biologicheskoi Khimii, 2024, Vol. 64, pp. 219-246.

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Muranov, K.O. Fenton Reaction in vivo and in vitro. Possibilities and Limitations. Biochemistry Moscow 89 (Suppl 1), S112–S126 (2024). https://doi.org/10.1134/S0006297924140074

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