Báo cáo khoa học: Simulation study of methemoglobin reduction in erythrocytes Differential contributions of two pathways to tolerance to oxidative stress

Simulation Study Of Methemoglobin Reduction in Erythrocytes

Authors: Ayako Kinoshita, Yoichi Nakayama, Tomoya Kitayama, Masaru Tomita

Field: Erythrocyte, Mathematical Modeling, Metabolism, Methemoglobin, Oxidative Stress

Document Content: This study presents a mathematical model to quantitatively assess the contributions of two primary methemoglobin (metHb)-reducing pathways in erythrocytes: the flavin-NADPH pathway and the cytb5-NADH pathway. MetHb, an oxidized form of hemoglobin, impairs oxygen transport and is continuously formed due to oxidative stress. Erythrocytes possess enzymatic systems to prevent its accumulation. The developed model integrates central energy metabolism to evaluate how these two pathways contribute to metHb reduction. Simulation results indicate that the flavin-NADPH pathway is dominant under normal physiological conditions, while the cytb5-NADH pathway becomes more significant when metHb levels are excessively high, exceeding the capacity of the flavin-NADPH system. This research explores the implications of having two distinct metHb-reducing pathways for tolerance to oxidative stress.

Detailed Table of Contents:

• Simulation of methemoglobin reduction
• Differential contributions of two pathways to tolerance to oxidative stress
• Keywords
• Correspondence
• Note
• Schematic representation of the pathways included in the model
• Simulation experiment of biological conditions
• Relative contribution of each pathway to metHb reduction as a function of the rate of metHb formation
• Discussion
• Mathematical model
• MetHb-reduction pathways
• Other pathways including the central carbon metabolism
• Acknowledgements
• References
• Supplementary material