Incorporating expression data in metabolic modeling: a case study of lactate dehydrogenase

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Publication:2202155

DOI10.1016/J.JTBI.2005.10.007zbMATH Open1447.92179arXivq-bio/0511013OpenAlexW2115852132WikidataQ33228429 ScholiaQ33228429MaRDI QIDQ2202155FDOQ2202155


Authors: Joshua Downer, Joel R. Sevinsky, Natalie G. Ahn, Katheryn A. Resing, M. D. Betterton Edit this on Wikidata


Publication date: 17 September 2020

Published in: Journal of Theoretical Biology (Search for Journal in Brave)

Abstract: Integrating biological information from different sources to understand cellular processes is an important problem in systems biology. We use data from mRNA expression arrays and chemical kinetics to formulate a metabolic model relevant to K562 erythroleukemia cells. MAP kinase pathway activation alters the expression of metabolic enzymes in K562 cells. Our array data show changes in expression of lactate dehydrogenase (LDH) isoforms after treatment with phorbol 12-myristate 13-acetate (PMA), which activates MAP kinase signaling. We model the change in lactate production which occurs when the MAP kinase pathway is activated, using a non-equilibrium, chemical-kinetic model of homolactic fermentation. In particular, we examine the role of LDH isoforms, which catalyze the conversion of pyruvate to lactate. Changes in the isoform ratio are not the primary determinant of the production of lactate. Rather, the total concentration of LDH controls the lactate concentration.


Full work available at URL: https://arxiv.org/abs/q-bio/0511013




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