Functional Consequences of Metabolic Zonation in Murine Livers: Insights for an Old Story
| Autor: | David Meierhofer, Johannes Eckstein, Hermann-Georg Holzhütter, Fritzi Ott, Nikolaus Berndt, Erik Kolbe, Madlen Matz-Soja, Robert Gajowski |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics 0301 basic medicine Primary Cell Culture Biology Mice 03 medical and health sciences 0302 clinical medicine Glutaminase Ammonia Glutamine synthetase Glucokinase Animals Amino Acids Shotgun proteomics Cells Cultured chemistry.chemical_classification Spatial Analysis Arginase Hepatology L-Lactate Dehydrogenase Fatty Acids Amino acid Glutamine Metabolic pathway 030104 developmental biology Enzyme Liver chemistry Biochemistry Models Animal Hepatocytes Carbohydrate Metabolism 030211 gastroenterology & hepatology 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit Drug metabolism |
| Zdroj: | Hepatology |
| Popis: | Background and aims Zone-dependent differences in expression of metabolic enzymes along the portocentral 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 important, an estimation of the associated functional differences between portal and central hepatocytes is missing thus far. Approach and results We addressed this problem by establishing a 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). Conclusions The model simulations revealed significant portal-to-central differences in almost all metabolic pathways involving carbohydrates, fatty acids, amino acids, and detoxification. |
| Databáze: | OpenAIRE |
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