title: A mechanistic kinetic description of lactate dehydrogenase elucidating cancer diagnosis and inhibitor evaluation.
abstract: As a key enzyme for glycolysis, lactate dehydrogenase (LDH) remains as a topic of great interest in cancer study. Though a number of kinetic models have been applied to describe the dynamic behavior of LDH, few can reflect its actual mechanism, making it difficult to explain the observed substrate and competitor inhibitions at wide concentration ranges. A novel mechanistic kinetic model is developed based on the enzymatic processes and the interactive properties of LDH. Better kinetic simulation as well as new enzyme interactivity information and kinetic properties extracted from published articles via the novel model was presented. Case studies were presented to a comprehensive understanding of the effect of temperature, substrate, and inhibitor on LDH kinetic activities for promising application in cancer diagnosis, inhibitor evaluation, and adequate drug dosage prediction.
authors.affiliation: a Department of Paper and Bioprocess Engineering , SUNY ESF , Syracuse , NY , USA.|b Biologics Process Development, Global Manufacturing and Supply , Bristol-Myers Squibb Company , Devens , MA , USA.
authors.forename: Peifeng
authors.initials: P
authors.lastname: Tang
authors.affiliation: b Biologics Process Development, Global Manufacturing and Supply , Bristol-Myers Squibb Company , Devens , MA , USA.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Xu
authors.affiliation: b Biologics Process Development, Global Manufacturing and Supply , Bristol-Myers Squibb Company , Devens , MA , USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Oliveira
authors.affiliation: b Biologics Process Development, Global Manufacturing and Supply , Bristol-Myers Squibb Company , Devens , MA , USA.
authors.forename: Zheng Jian
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: a Department of Paper and Bioprocess Engineering , SUNY ESF , Syracuse , NY , USA.
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009369:Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000378:metabolism; D013696:Temperature
chemical_list: D004791:Enzyme Inhibitors; D007770:L-Lactate Dehydrogenase
keywords: Cancer diagnosis; inhibitor evaluation; kinetic model; lactate dehydrogenase; oligomeric enzyme