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Simulation study of methemoglobin reduction in erythrocytes
Author(s) -
Kinoshita Ayako,
Nakayama Yoichi,
Kitayama Tomoya,
Tomita Masaru
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05685.x
Subject(s) - methemoglobin , hemoglobin , chemistry , flavin group , oxidative phosphorylation , biophysics , nitrite , biochemistry , oxidative stress , heme , redox , biology , enzyme , inorganic chemistry , organic chemistry , nitrate
Methemoglobin (metHb), an oxidized form of hemoglobin, is unable to bind and carry oxygen. Erythrocytes are continuously subjected to oxidative stress and nitrite exposure, which results in the spontaneous formation of metHb. To avoid the accumulation of metHb, reductive pathways mediated by cytochrome b 5 or flavin, coupled with NADH‐dependent or NADPH‐dependent metHb reductases, respectively, keep the level of metHb in erythrocytes at less than 1% of the total hemoglobin under normal conditions. In this work, a mathematical model has been developed to quantitatively assess the relative contributions of the two major metHb‐reducing pathways, taking into consideration the supply of NADH and NADPH from central energy metabolism. The results of the simulation experiments suggest that these pathways have different roles in the reduction of metHb; one has a high response rate to hemoglobin oxidation with a limited reducing flux, and the other has a low response rate with a high capacity flux. On the basis of the results of our model, under normal oxidative conditions, the NADPH‐dependent system, the physiological role of which to date has been unclear, is predicted to be responsible for most of the reduction of metHb. In contrast, the cytochrome b 5–NADH pathway becomes dominant under conditions of excess metHb accumulation, only after the capacity of the flavin–NADPH pathway has reached its limit. We discuss the potential implications of a system designed with two metHb‐reducing pathways in human erythrocytes.