Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition

Yoichi Nakayama, Ayako Kinoshita, Masaru Tomita

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Cell simulation, which aims to predict the complex and dynamic behavior of living cells, is becoming a valuable tool. In silico models of human red blood cell (RBC) metabolism have been developed by several laboratories. An RBC model using the E-Cell simulation system has been developed. This prototype model consists of three major metabolic pathways, namely, the glycolytic pathway, the pentose phosphate pathway and the nucleotide metabolic pathway. Like the previous model by Joshi and Palsson, it also models physical effects such as osmotic balance. This model was used here to reconstruct the pathology arising from hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is the most common deficiency in human RBC. Results: Since the prototype model could not reproduce the state of G6PD deficiency, the model was modified to include a pathway for de novo glutathione synthesis and a glutathione disulfide (GSSG) export system. The de novo glutathione (GSH) synthesis pathway was found to compensate partially for the lowered GSH concentrations resulting from G6PD deficiency, with the result that GSSG could be maintained at a very low concentration due to the active export system. Conclusion: The results of the simulation were consistent with the estimated situation of real G6PD-deficient cells. These results suggest that the de novo glutathione synthesis pathway and the GSSG export system play an important role in alleviating the consequences of G6PD deficiency.

Original languageEnglish
JournalTheoretical Biology and Medical Modelling
Volume2
DOIs
Publication statusPublished - 2005 May 9

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Glucosephosphate Dehydrogenase Deficiency
Red Blood Cells
Glutathione Disulfide
Metabolism
Dynamic Simulation
Phosphate
Pathway
Blood
Erythrocytes
Cells
Glucose
Glutathione
Phosphates
Computer simulation
Metabolic Networks and Pathways
Pentose Phosphate Pathway
Cell
Synthesis
Glucosephosphate Dehydrogenase
Model

ASJC Scopus subject areas

  • Health Informatics
  • Medicine(all)

Cite this

Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. / Nakayama, Yoichi; Kinoshita, Ayako; Tomita, Masaru.

In: Theoretical Biology and Medical Modelling, Vol. 2, 09.05.2005.

Research output: Contribution to journalArticle

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