title: Incorporating expression data in metabolic modeling: a case study of lactate dehydrogenase.
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 catalyse 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.
authors.affiliation: Department of Applied Mathematics, University of Colorado at Boulder, 526 UCB, CO 80309-0526, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Downer
authors.forename: Joel R
authors.initials: JR
authors.lastname: Sevinsky
authors.forename: Natalie G
authors.initials: NG
authors.lastname: Ahn
authors.forename: Katheryn A
authors.initials: KA
authors.lastname: Resing
authors.forename: M D
authors.initials: MD
authors.lastname: Betterton
mesh_terms: D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004912:Erythrocytes / Q000378:metabolism; D005285:Fermentation; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D045022:Lactate Dehydrogenases / Q000378:metabolism*; D019344:Lactic Acid / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008956:Models, Chemical; D019289:Pyruvic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D019344:Lactic Acid; D019289:Pyruvic Acid; D045022:Lactate Dehydrogenases; D013755:Tetradecanoylphorbol Acetate