Role of thiamine thiol form in nitric oxide metabolism

Abstract

In alkaline media the thiamine cyclic form is converted into a thiol form (pK(a) 9.2) with an opened thiazole ring. The thiamine thiol form releases nitric oxide from S-nitrosoglutathione (GSNO). Thiamine disulfide, mixed thiamine disulfide with glutathione, and nitric oxide are produced in the reaction. Free glutathione was recorded in small amounts. The concentration of formed nitric oxide agreed well with the concentration of degraded GSNO. The concentration of released nitric oxide was determined under anaerobic conditions spectrophotometrically by production of nitrosohemoglobin. In air, the release of nitric oxide was recorded by the production of nitrite or the oxidation of oxyhemoglobin to methemoglobin. The concentration of the thiol form in the body under physiological pH values (7.2-7.4) did not exceed 1.5-2.0%. We believe that due to the exchange reactions between the thiamine thiol form and S-nitrosocysteine protein residues, nitric oxide can be released and mixed thiamine-protein disulfides are formed. The mixed thiamine disulfides (including thiamine ester disulfides) as well as the thiamine disulfide form are quite easily reduced by low molecular weight thiols to form the thiamine cyclic form with a closed thiazole ring. A possible role of the thiamine thiol form in releasing deposited nitric oxide from low-molecular-weight S-nitrosothiols and protein S-nitrosothiols and in regulation of blood flow in the vascular bed is discussed.

Maillard reaction of ribose 5-phosphate generates superoxide and glycation products for bovine heart cytochrome c reduction

“…In both cases, these results were similar to those of Stepuro et al11 using glucose and amino acids except that observable cytochrome c reduction by the R5P reaction was immediate and required no long-term pre-incubation of sugar and amine to obtain significant reductions. The cytochrome c reduction rate observed is directly related to the concentrations of R5P and amine (in the first system the participating amines are lysines on the cytochrome c molecule itself) and on the pK a value(s) of the attacking amines.…”

“…Many of these solutions in long-term reactions (up to 24 h) showed biphasic reaction profiles with a fast initial reduction and then slower rates of reduction (see Supplementary Data, Figure S4). As shown by other studies, sugars like glucose, glucose 6-phosphate, and fructose 6-phosphate failed to cause full reductions at the mM levels employed 11. The R5P and ribose plus phosphate reactions did not exhibit these biphasic rate profiles.…”

“…In further support, the cytochrome reduction rate shows a good correlation with the p K a of the attacking amine when a series of monoamines are compared (see Figure 3). As shown by Stepuro et al11 for a series of amino acids, however, other factors must be involved that change the glycation rate and affect the subsequent cytochrome c reduction potential of these compounds. It appears that some type of synergism occurs, for example, for molecules like Lys that contain more than a single amine.…”

“…Using methylglyoxal in a Maillard glycation reaction, Lee et al8 and Yim et al6, 9, 10 also reported the direct transfer of an electron to O 2 from a cross-linked Schiff base (via a dicarbonyl), ultimately forming a stable free-radical cation. Stepuro et al11 likewise observed reduction of cytochrome c by high levels of glucose after extended times (up to 2 weeks) at 37 °C. They ascribed the reduction of cytochrome c to a combination of O 2 - and post-Amadori glycation products, again implicating dicarbonyls and ketoamines in the process.…”

"Infusão de glicose e tiamina em ratos tratados com dose aguda de etanol"

“…A glutationa oxidada pela ligação com espécies radicalares é reconvertida à forma reduzida por ligação com a forma tiol da tiamina formando uma ponte dissulfeto com a mesma, desativando a espécie radicalar e restaurando a glutationa reduzida (Stepuro, Piletskaya et al, 2005). Shadyro et al (2005) verificaram a supressão da formação de MDA à partir da peroxidação lipídica iniciada pelo radical hidroxietila, postulando que o grupamento amino, ligado ao anel aromático da tiamina, é um sítio de reação e desativação do radical hidroxietila.…”