title: The space of enzyme regulation in HeLa cells can be inferred from its intracellular metabolome.
abstract: During the transition from a healthy state to a cancerous one, cells alter their metabolism to increase proliferation. The underlying metabolic alterations may be caused by a variety of different regulatory events on the transcriptional or post-transcriptional level whose identification contributes to the rational design of therapeutic targets. We present a mechanistic strategy capable of inferring enzymatic regulation from intracellular metabolome measurements that is independent of the actual mechanism of regulation. Here, enzyme activities are expressed by the space of all feasible kinetic constants (k-cone) such that the alteration between two phenotypes is given by their corresponding kinetic spaces. Deriving an expression for the transformation of the healthy to the cancer k-cone we identified putative regulated enzymes between the HeLa and HaCaT cell lines. We show that only a few enzymatic activities change between those two cell lines and that this regulation does not depend on gene transcription but is instead post-transcriptional. Here, we identify phosphofructokinase as the major driver of proliferation in HeLa cells and suggest an optional regulatory program, associated with oxidative stress, that affects the activity of the pentose phosphate pathway.
authors.affiliation: Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico.
authors.forename: Christian
authors.initials: C
authors.lastname: Diener
authors.affiliation: Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico.
authors.forename: Felipe
authors.initials: F
authors.lastname: Muñoz-Gonzalez
authors.affiliation: Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca 62210, México.
authors.forename: Sergio
authors.initials: S
authors.lastname: Encarnación
authors.affiliation: Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico.|Coordinación de la Investigación Científica - Red de Apoyo a la Investigación UNAM, Mexico.
authors.forename: Osbaldo
authors.initials: O
authors.lastname: Resendis-Antonio
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D019075:Electrophoresis, Capillary; D004798:Enzymes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D055442:Metabolome; D025221:Phosphofructokinases / Q000378:metabolism
chemical_list: D004798:Enzymes; D025221:Phosphofructokinases