Emerging Roles for Metabolic Engineering - Understanding Primitive and Complex Metabolic Models and Their Relevance to Healthy and Diseased Kidney Podocytes

Jochen      Reiser; Mehmet   M.   Altintas; Kutlu   O.   Ulgen; Darryl      Palmer-Toy; Vivian   E.   Shih; Dhinakar   S.   Kompala

Abstract

The central metabolism of a cell can determine its short- and long-term structure and function. When a disease state arises, the metabolism (i.e., the transportation of nutrients into the cells, the overall substrate utilization and production, synthesis and accumulation of intracellular metabolites, etc.) is altered in a way that may permit organisms to survive under the changing physiologic constraints. Although the response of cells to injury was studied thoroughly using molecular biology and structural morphology techniques, the knowledge regarding the metabolic signatures of the disease is limited. However, recent advances in analytical methods and mathematical tools have led to new approaches to those questions with the concept of computational biology which relies on the integration of experimentation, data processing and modeling. The attempt to formulate current knowledge in mathematical terms has led to the development of several mathematical modeling tools (i.e., metabolic flux analysis, metabolic control analysis, etc.) that helps us to understand an entire biological system from basic structure to dynamic interactions. This review provides an overview and summarizes the current status of applications of mathematical models for the quantification of fluxes. A specific example of kidney podocyte cells illustrates how metabolic alterations, which occur during injury, can be used to aid in future therapeutic development.

Keywords: Metabolic flux analysis, intracellular fluxes, podocyte metabolism, analysis of the health and disease

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