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Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites
Department of Anesthesia, University of California, San Francisco, CA 94143, USA
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
* Author to whom correspondence should be addressed.
Received: 18 August 2011; in revised form: 13 September 2011 / Accepted: 21 September 2011 / Published: 28 September 2011
Abstract: Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing “omics”-based, diagnostic tests to help influence therapies.
Keywords: metabolomics; metabonomics; oxidative stress; NMR; proteomics; transcriptionomics; multivariate analysis; Principal Component Analysis; targeted profiling; chemometrics; brain; liver; kidney; heart
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MDPI and ACS Style
Liu, J.; Litt, L.; Segal, M.R.; Kelly, M.J.S.; Pelton, J.G.; Kim, M. Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites. Int. J. Mol. Sci. 2011, 12, 6469-6501.
Liu J, Litt L, Segal MR, Kelly MJS, Pelton JG, Kim M. Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites. International Journal of Molecular Sciences. 2011; 12(10):6469-6501.
Liu, Jia; Litt, Lawrence; Segal, Mark R.; Kelly, Mark J. S.; Pelton, Jeffrey G.; Kim, Myungwon. 2011. "Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites." Int. J. Mol. Sci. 12, no. 10: 6469-6501.