Karen van Eunen

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About Karen van Eunen:

I work as a project manager for the Innovative Training Network PoLiMeR - Polymers in the LIver: Metabolism and Regulation funded by the EU. In addition I am a project manager for the UMCG Research BV where I support scientist in the pre-award phase with writing their proposals and in the post-award phase with managing their awarded projects.

SEEK ID: https://fairdomhub.org/people/1229

Location: Netherlands

ORCID: Not specified

Joined: 15th Jan 2019

Expertise: Systems Biology, enzyme kinetics, Molecular Biology, Dynamic modelling, dynamics of biological networks., Metabolic Control Analaysis, Project Management

Tools: ODE, Enzyme assay, enzymatic analyses, Cell culture

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PoLiMeR - Polymers in the Liver: Metabolism and Regulation

PoLiMeR is funded through the EU Marie Skłodowska-Curie Innovative Training Network (ITN), which drives scientific excellence and innovation. ITNs bring together universities, research institutes, industry and clinical partners from across the world to train researchers to doctorate level.

Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease ...

Programme: This Project is not associated with a Programme

Public web page: http://polimer-itn.eu/

Organisms: Homo sapiens, Mus musculus, Rattus norvegicus

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University of Groningen

Country: Netherlands

City: Groningen

Web page: http://www.rug.nl/corporate/index

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Kinetics Minireviews

PoLiMeR - Polymers in the Liver: Metabolism and Regulation

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Minireviews about each enzyme in the mitochindrial beta-oxidation model on which the final parameter choices (fixed-parameter model) and parameter sampling distributions (ensemble) were based.

Submitter: Christoff Odendaal

Biological problem addressed: Model Analysis Type

Investigation: Mitochondrial fatty acid oxidation in human liver

Study: Model construction

Organisms: No organisms

Models: No Models

SOPs: Parameter Search SOP

Data files: No Data files

Snapshots: Snapshot 1

DOI: 10.15490/fairdomhub.1.assay.2137.1

Created: 7th Jul 2023 at 10:41, Last updated: 3rd Mar 2024 at 08:10

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Personalised modelling of clinical heterogeneity between medium-chain acyl-CoA dehydrogenase patients.

PoLiMeR - Polymers in the Liver: Metabolism and Regulation

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Abstract (Expand)

BACKGROUND: Monogenetic inborn errors of metabolism cause a wide phenotypic heterogeneity that may even differ between family members carrying the same genetic variant. Computational modelling of … metabolic networks may identify putative sources of this inter-patient heterogeneity. Here, we mainly focus on medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the most common inborn error of the mitochondrial fatty acid oxidation (mFAO). It is an enigma why some MCADD patients-if untreated-are at risk to develop severe metabolic decompensations, whereas others remain asymptomatic throughout life. We hypothesised that an ability to maintain an increased free mitochondrial CoA (CoASH) and pathway flux might distinguish asymptomatic from symptomatic patients. RESULTS: We built and experimentally validated, for the first time, a kinetic model of the human liver mFAO. Metabolites were partitioned according to their water solubility between the bulk aqueous matrix and the inner membrane. Enzymes are also either membrane-bound or in the matrix. This metabolite partitioning is a novel model attribute and improved predictions. MCADD substantially reduced pathway flux and CoASH, the latter due to the sequestration of CoA as medium-chain acyl-CoA esters. Analysis of urine from MCADD patients obtained during a metabolic decompensation showed an accumulation of medium- and short-chain acylcarnitines, just like the acyl-CoA pool in the MCADD model. The model suggested some rescues that increased flux and CoASH, notably increasing short-chain acyl-CoA dehydrogenase (SCAD) levels. Proteome analysis of MCADD patient-derived fibroblasts indeed revealed elevated levels of SCAD in a patient with a clinically asymptomatic state. This is a rescue for MCADD that has not been explored before. Personalised models based on these proteomics data confirmed an increased pathway flux and CoASH in the model of an asymptomatic patient compared to those of symptomatic MCADD patients. CONCLUSIONS: We present a detailed, validated kinetic model of mFAO in human liver, with solubility-dependent metabolite partitioning. Personalised modelling of individual patients provides a novel explanation for phenotypic heterogeneity among MCADD patients. Further development of personalised metabolic models is a promising direction to improve individualised risk assessment, management and monitoring for inborn errors of metabolism.

Authors: C. Odendaal, E. A. Jager, A. M. F. Martines, M. A. Vieira-Lara, N. C. A. Huijkman, L. A. Kiyuna, A. Gerding, J. C. Wolters, R. Heiner-Fokkema, K. van Eunen, T. G. J. Derks, B. M. Bakker

Date Published: 4th Sep 2023

Publication Type: Journal

PubMed ID: 37667308

Citation: BMC Biol. 2023 Sep 4;21(1):184. doi: 10.1186/s12915-023-01652-9.

Created: 28th Feb 2024 at 06:36

Living on the edge: substrate competition explains loss of robustness in mitochondrial fatty-acid oxidation disorders.

PoLiMeR - Polymers in the Liver: Metabolism and Regulation

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BACKGROUND: Defects in genes involved in mitochondrial fatty-acid oxidation (mFAO) reduce the ability of patients to cope with metabolic challenges. mFAO enzymes accept multiple substrates of different …

Authors: K. van Eunen, C. M. Volker-Touw, A. Gerding, A. Bleeker, J. C. Wolters, W. J. van Rijt, A. M. Martines, K. E. Niezen-Koning, R. M. Heiner, H. Permentier, A. K. Groen, D. J. Reijngoud, T. G. Derks, B. M. Bakker