Computational Systems Biochemistry Group

Nitrogen in the lobulus

Urea production is located only in the periportal fraction of hepatocytes in the liver lobule structure. Ammonia clearence is concentrated at the pericentral fraction. Glutamine functions as an intermediate carrier of nitrogen in this process. The questions that arise are "Why?" and "How?"^*

Heterogenous liver

Also processes such as heme synthesis have been identified to be unevenely distributed in the hepatic tissue. This suggsts a completely different metabolism in the different fractions of hepatocytes.

Consequences

Consequently, the metabolic function of the liver can not be fully understood investigating just one hepatocyte. Here, a multi-hepatocyte large-scale flux-balance model will be set up.

Parametrization

Such a model has many degrees of freedom and to avoid trivial and unphysiological predictions constraints must be used. These constraints will be based on reference flux solution obtained with the methods of another VLN project in our group (Metabolic flux changes). The information source are experiments where the liver tissue is fractionized in periportal and pericentral hepatocytes and their RNA expression is measured used to obtain reference solutions.

Cooperation

Finally, the predicted flux distribution of the multicellular model are analyzed to propose further mechanisms of cooperation between the cells. The heterogenous expression of the enzymes involved will then be verified with more focused experiments.

Flouresence-labeled imaging

With flourecence-labeled antibodies it is possible to image certain crucial proteins in the tissue context allowing a final proof of lobular dishomogenity.

Footnote

^* This particular system is investigated in another VLN project.

Note

This project is part of Virtual Liver, a major national initiative funded by the German Federal Ministry for Education and Research (BMBF) and is connected to WP subprojects A1.1, A1.2, A1.3, B2.2, and C3.

Researchers

Prof. Hermann-Georg Holzhütter
Dr. Andreas Hoppe
Matthias König
(Sascha Bulik)

		Zonation of Hepatocyte Metabolism
Home Research VirtualLiver People Publications Software Positions Events Contact		Nitrogen in the lobulus Urea production is located only in the periportal fraction of hepatocytes in the liver lobule structure. Ammonia clearence is concentrated at the pericentral fraction. Glutamine functions as an intermediate carrier of nitrogen in this process. The questions that arise are "Why?" and "How?"^* Heterogenous liver Also processes such as heme synthesis have been identified to be unevenely distributed in the hepatic tissue. This suggsts a completely different metabolism in the different fractions of hepatocytes. Consequences Consequently, the metabolic function of the liver can not be fully understood investigating just one hepatocyte. Here, a multi-hepatocyte large-scale flux-balance model will be set up. Parametrization Such a model has many degrees of freedom and to avoid trivial and unphysiological predictions constraints must be used. These constraints will be based on reference flux solution obtained with the methods of another VLN project in our group (Metabolic flux changes). The information source are experiments where the liver tissue is fractionized in periportal and pericentral hepatocytes and their RNA expression is measured used to obtain reference solutions. Cooperation Finally, the predicted flux distribution of the multicellular model are analyzed to propose further mechanisms of cooperation between the cells. The heterogenous expression of the enzymes involved will then be verified with more focused experiments. Flouresence-labeled imaging With flourecence-labeled antibodies it is possible to image certain crucial proteins in the tissue context allowing a final proof of lobular dishomogenity. Footnote ^* This particular system is investigated in another VLN project. Note This project is part of Virtual Liver, a major national initiative funded by the German Federal Ministry for Education and Research (BMBF) and is connected to WP subprojects A1.1, A1.2, A1.3, B2.2, and C3. Researchers Prof. Hermann-Georg Holzhütter Dr. Andreas Hoppe Matthias König (Sascha Bulik)