Oxidation of thiamine on reaction with nitrogen dioxide generated by ferric myoglobin and hemoglobin in the presence of nitrite and hydrogen peroxide

Abstract

It is shown that nitrogen dioxide oxidizes thiamine to thiamine disulfide, thiochrome, and oxodihydrothiochrome (ODTch). The latter is formed during oxidation of thiochrome by nitrogen dioxide. Nitrogen dioxide was produced by incubation of nitrite with horse ferric myoglobin and human hemoglobin in the presence of hydrogen peroxide. After addition of tyrosine or phenol to aqueous solutions containing oxoferryl forms of the hemoproteins, thiamine, and nitrite, the yield of thiochrome greatly increased, whereas the yield of ODTch decreased. In the presence of high concentrations of tyrosine or phenol compounds ODTch was not formed at all. The neutral form of thiamine with the closed thiazole cycle and minor tricyclic form of thiamine do not enter the heme pocket of the protein and do not interact with the oxoferryl heme complex Fe(IV=O) or porphyrin radical. The tricyclic form of thiamine is oxidized to thiochrome by tyrosyl radicals located on the surface of the hemoprotein. The thiol form of thiamine is oxidized to thiamine disulfide by both hemoprotein tyrosyl radicals and oxoferryl heme complexes. Nitrite and also tyrosine, tyramine, and phenol readily penetrate into the heme pocket of the protein and reduce the oxyferryl complex to ferric cation. These reactions yield nitrogen dioxide as well as tyrosyl and phenoxyl radicals of tyrosine molecules and phenol compounds, respectively. Tyrosyl and phenoxyl radicals of low molecular weight compounds oxidize thiamine only to thiochrome and thiamine disulfide. The effect of oxoferryl forms of myoglobin and hemoglobin, nitrogen dioxide, and phenol on thiamine oxidative transformation as well as antioxidant properties of the hydrophobic thiamine metabolites thiochrome and ODTch are discussed.

Activation of Mitochondrial 2-Oxoglutarate Dehydrogenase by Cocarboxylase in Human Lung Adenocarcinoma Cells A549 Is p53/p21-Dependent and Impairs Cellular Redox State, Mimicking the Cisplatin Action

“…A medically important contribution of the present work is the demonstration of a strong negative effect of a high dose of ThDP (known in medicine as cocarboxylase) on the viability of the adenocarcinoma epithelial cell line A549, which is not observed in a non-cancer epithelium cell line (Figure 6), nor acknowledged in any previous studies on the effects of ThDP and its precursor thiamine in a number of chemical [59,60] and biological systems [33][34][35][36][37]. After the incubation with 5 mM ThDP for 24 h, the viability impairment in A549 cells is manifested as a 70% decrease in cellular NAD(P)H:XTT reductase activity and 20-30% lower levels of cellular glutathione (Figure 6), accompanied by a 30% reduction of the glutathione redox potential (GSH/GSSG, Table 1) in A549 wt cells.…”

Influence of Anticoagulants on Determination of H2O2 Levels in Blood: Comparison of Citrate and EDTA

“…Inhibition or stimulation of oxidation via the Fenton reaction perhaps depends on the ratio of EDTA to iron. A ratio of EDTA to iron that is higher than 1:1 inhibits oxidation, while lower ratios stimulate it [11]. Studies by Baron,et al [2] support this, as the 1:1 of EDTA/iron ratio in their study resulted in stimulation of protein oxidation.…”

“…It is pertinent to since it has been observed that in the presence of Fe 2+ and H 2 O 2 , thiochrome was oxidized, while the addition of excess EDTA resulted in inhibition of oxidation, possibly due to the chelation of iron with EDTA [7][8][9][10][11]. Akagawa and Suyama reported similar results, where oxidation via the Fenton reaction, in this case, of H 2 O 2 and Cu 2+ had inhibition through action of EDTA.…”

Characterization of thiamine uptake and utilization in Candida spp. subjected to oxidative stress

“…In particular, thiamine can confer the resistance against oxidative agents in plants and bacteria (Jung & Kim, 2003;Tunc-Ozdemir et al, 2009;Rapala-Kozik et al, 2012) and, in forms of thiamine triphosphate and its adenylated derivatives, it can also serve as a signaling molecule under stress conditions (Lakaye et al, 2004;Gigliobianco et al, 2010). Although the mechanisms of the protective action of thiamine has not yet been recognized, the proposed thiamine oxidation upon the contact with free radicals can result in formation of thiamine thiols and tricyclic thiochrome derivatives (Lukienko et al, 2000;Stepuro et al, 2012).…”