Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Diener, C; Muñoz-Gonzalez, F; Encarnación, S; Resendis-Antonio, O.
The space of enzyme regulation in HeLa cells can be inferred from its intracellular metabolome.
Sci Rep. 2016; 6: 28415
Doi: 10.1038/srep28415
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- Leading authors Med Uni Graz
- Diener Christian
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line - administration & dosage
- Cell Proliferation - administration & dosage
- Electrophoresis, Capillary - administration & dosage
- Enzymes - metabolism
- Gene Expression Regulation - administration & dosage
- HeLa Cells - administration & dosage
- Humans - administration & dosage
- Kinetics - administration & dosage
- Mass Spectrometry - administration & dosage
- Metabolome - administration & dosage
- Phosphofructokinases - metabolism