Proposed Mechanism of Nitrite-Induced Methemoglobinemia

  title={Proposed Mechanism of Nitrite-Induced Methemoglobinemia},
  author={Vladimir Titov and Yu. M. Petrenko},
  journal={Biochemistry (Moscow)},
A scheme of development of nitrite-induced oxyhemoglobin oxidation in erythrocytes based on the analysis of experimental data is proposed. It was found that, contrary to widespread opinion, direct oxidative-reductive interaction between hemoglobin and nitrite is absent or negligible under physiological conditions. The driving stage of this process is methemoglobin-catalyzed peroxidase oxidation of nitrite. The product of the oxidation (presumably NO2·) directly oxidizes oxyhemoglobin to… 

The Reaction between Nitrite and Oxyhemoglobin

It is shown that none of the previously published mechanisms is sufficient to fully explain the kinetics of the reaction of nitrite with oxyhemoglobin, and a new model is proposed that combines the roles of H2O2 and NO2 in the reaction mechanism and is consistent with experimental data.

Methemoglobin—It's not just blue: A concise review

  • J. Umbreit
  • Biology, Medicine
    American journal of hematology
  • 2007
Hemoglobin has functions besides carrying oxygen to the tissues, and regulates vascular tone and inflammation via a redox couple with methemoglobin, paralleled by the well‐described role in the oxidation of various drugs resulting in methemoglobinemia.

Mechanism of inhibition of catalase by nitro and nitroso compounds

DNIC with thiolate ligands and S-nitrosothiols, which are NO and NO+ donors, share the earlier demonstrated ability of nitrite for inhibition of catalase, and this fact suggests that NO+ ions rather than neutral NO molecules are responsible for the enzyme inactivation due to nitrosation of its structures.

Nitrite and nitroso compounds can serve as specific catalase inhibitors

  • V. TitovA. Osipov
  • Chemistry
    Redox report : communications in free radical research
  • 2017
Evidence is presented that nitrite and nitrosothiols, nitrosoamines and non-heme dinitrosyl iron complexes can reversibly inhibit catalase with equal effectiveness and it is proposed that the directCatalase inhibitor is a positively charged NO-group.

Detecting Methemoglobinemia in Animals with a Drop of Blood

A procedure to quickly determine methemoglobin levels in mammals and birds can be estimated with one standard curve from any animal species and an image of a blood spot, and will be useful during field studies, in agricultural areas, or in a veterinarian's office for the rapid diagnosis of methemoglobinemia in non-target animals that have eaten toxicants/baits or baited animals.


The diagnosis and management of a patient with acquired methemoglobinemia as a result of dapsone use for certain skin condition is described.

Acquired Methemoglobinemia- An Overview

One hundred thirty-eight cases of acquired methemoglobinemia were detected over 28 months and there were no gender predisposition and performed over a wide range of age (Patient aged 4 days to 86 years).

Crystallographic trapping of heme loss intermediates during the nitrite-induced degradation of human hemoglobin.

Structural insight is provided into a possible pathway for nitrite-induced loss of heme from human Hb and regiospecific nitration of the heme at the 2-vinyl position is shown.



A mechanism for the conversion of oxyhemoglobin to methemoglobin by nitrite.

The autocatalytic nature of the overall reaction in the presence of excess nitrite is the result of metHb, which is formed in both parts of the reaction, associating with nitrite to increase the concentration of one reactant of the cyanide-sensitive part.

Nitrite–Catalase Interaction as an Important Element of Nitrite Toxicity

The naturally existing gradient of chloride and other anion concentrations between intra- and extracellular media appears to be the most important mechanism of cell protection from inhibition of intracellular catalase by nitrite, and possible mechanisms of this inhibition are discussed.

Generation of NO during oxidation of hemoglobin ferroforms by nitrite.

The incubation of deoxyHb with S-nitrosoglutathione resulted in its complete conversion to nitrosoHb, and this indicated that NO was released during the spontaneous decomposition of GSNO, and the generation of metHb in the solution.

Reaction of Human Hemoglobin with Peroxynitrite

A role of oxyhemoglobin as a relevant intravascular sink of peroxynitrite is supported as well as a reaction mechanism that involves the net one-electron oxidation of the ferrous heme, isomerization of per oxynitrites to nitrate, and production of superoxide radical and hydrogen peroxide.