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  Functional consequences of metabolic zonation in murine livers: New insights for an old story

Berndt, N., Kolbe, E., Gajowski, R., Eckstein, J., Ott, F., Meierhofer, D., et al. (in press). Functional consequences of metabolic zonation in murine livers: New insights for an old story. Hepatology, HEP-19-1360. doi:10.1002/hep.31274.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-40B4-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-40B5-5
Genre: Journal Article

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Berndt2020_accepted manuscript.pdf (Preprint), 19MB
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Berndt2020_accepted manuscript.pdf
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© 2020 American Association for the Study of Liver Diseases
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 Creators:
Berndt, Nikolaus , Author
Kolbe, Erik, Author
Gajowski, Robert1, Author              
Eckstein, Johannes, Author
Ott, Fritzi, Author
Meierhofer, David1, Author              
Holzhütter, Hermann Georg , Author
Matz‐Soja, Madlen , Author
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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Free keywords: HEPATOKIN, metabolic zonation, hepatocytes, FACS, periportal, pericentral
 Abstract: Background & Aims Zone‐dependent differences in the expression of metabolic enzymes along the porto‐central axis of the acinus are a long‐known feature of liver metabolism. A prominent example is the preferential localization of the enzyme glutamine synthetase in pericentral hepatocytes, where it converts potentially toxic ammonia to the valuable amino acid glutamine. However, with the exception of a few key regulatory enzymes, a comprehensive and quantitative assessment of zonal differences in the abundance of metabolic enzymes and much more importantly, an estimation of the associated functional differences between portal and central hepatocytes is missing thus far. Approach & Results We addressed this problem by establishing a new method for the separation of periportal and pericentral hepatocytes that yields sufficiently pure fractions of both cell populations. Quantitative shotgun proteomics identified hundreds of differentially expressed enzymes in the two cell populations. We used zone‐specific proteomics data for scaling of the maximal activities to generate portal and central instantiations of a comprehensive kinetic model of central hepatic metabolism (Hepatokin1). Conclusion The model simulations revealed significant portal‐to‐central differences in almost all metabolic pathways involving carbohydrates, fatty acids, amino acids and detoxification.

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Language(s): eng - English
 Dates: 2020-04-14
 Publication Status: Accepted / In Press
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1002/hep.31274
 Degree: -

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Title: Hepatology
Source Genre: Journal
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Publ. Info: Baltimore, Md. : John Wiley & Sons, Inc.
Pages: - Volume / Issue: - Sequence Number: HEP-19-1360 Start / End Page: - Identifier: ISSN: 0270-9139 (print)
ISSN: 1527-3350 (electronic)
CoNE: https://pure.mpg.de/cone/journals/resource/954925502190