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Critical Reviews™ in Biomedical Engineering
SJR: 0.207 SNIP: 0.376 CiteScore™: 0.79

ISSN Print: 0278-940X
ISSN Online: 1943-619X

Critical Reviews™ in Biomedical Engineering

DOI: 10.1615/CritRevBiomedEng.v39.i6.30
pages 511-534

Advanced Stoichiometric Analysis of Metabolic Networks of Mammalian Systems

Mehmet A. Orman
Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA
Francois Berthiaume
Department of Biomedical Engineering, Rutgers University, New Brunswick, New Jersey, USA
Ioannis P. Androulakis
Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, New Jersey; Biomedical Engineering Department, Rutgers University, Piscataway, New Jersey; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
Marianthi G. Ierapetritou
Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

ABSTRACT

Metabolic engineering tools have been widely applied to living organisms to gain a comprehensive understanding about cellular networks and to improve cellular properties. Metabolic flux analysis (MFA), flux balance analysis (FBA), and metabolic pathway analysis (MPA) are among the most popular tools in stoichiometric network analysis. Although application of these tools into well-known microbial systems is extensive in the literature, various barriers prevent them from being utilized in mammalian cells. Limited experimental data, complex regulatory mechanisms, and the requirement of more complex nutrient media are some major obstacles in mammalian cell systems. However, mammalian cells have been used to produce therapeutic proteins, to characterize disease states or related abnormal metabolic conditions, and to analyze the toxicological effects of some medicinally important drugs. Therefore, there is a growing need for extending metabolic engineering principles to mammalian cells in order to understand their underlying metabolic functions. In this review article, advanced metabolic engineering tools developed for stoichiometric analysis including MFA, FBA, and MPA are described. Applications of these tools in mammalian cells are discussed in detail, and the challenges and opportunities are highlighted.