A5063009717- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolomics and Mass Spectrometry Studies
- Cardiovascular and exercise physiology
- Adipose Tissue and Metabolism
- Cardiovascular Function and Risk Factors
- Microbial Metabolic Engineering and Bioproduction
- Metabolism and Genetic Disorders
- Gene Regulatory Network Analysis
- Pharmacogenetics and Drug Metabolism
- Muscle metabolism and nutrition
- Advanced MRI Techniques and Applications
- Neurofibromatosis and Schwannoma Cases
- Enzyme Catalysis and Immobilization
- Cardiac Ischemia and Reperfusion
- Bioinformatics and Genomic Networks
- Ion Transport and Channel Regulation
- Protein Structure and Dynamics
- Cardiovascular Effects of Exercise
- Electrochemical sensors and biosensors
- Electron Spin Resonance Studies
- Cellular transport and secretion
- Cardiomyopathy and Myosin Studies
- Mass Spectrometry Techniques and Applications
- Enzyme function and inhibition
Woodward (United States)
2022
Telemedicine & Advanced Technology Research Center
2018-2021
Henry M. Jackson Foundation
2019-2021
United States Army Medical Research and Development Command
2018-2021
University of Michigan
2014-2018
Michigan United
2018
Medical College of Wisconsin
2007-2013
Bioengineering Center
2007-2011
Eindhoven University of Technology
2009
University of Washington
2002-2006
A computational model of mitochondrial metabolism and electrophysiology is introduced applied to analysis data from isolated cardiac mitochondria on phosphate metabolites in striated muscle vivo. This constructed based detailed kinetics thermodynamically balanced reaction mechanisms a strict accounting rapidly equilibrating biochemical species. Since building such requires introducing large number adjustable kinetic parameters, correspondingly amount independent respiring different...
Systems for describing myocardial cellular metabolism with appropriate thermodynamic constraints on reactions have to be the basis of estimates intracellular and mitochondrial concentrations metabolites as driving forces reactions. This requires that tissue composition itself must modeled, but there is marked inconsistency in literature no full data set hearts any species. To formulate a self-consistent information densities, contents, or chemical components volumes spaces, we drew mostly...
Abstract The typical cause of death in pulmonary hypertension ( PH ) is right ventricular RV failure, with females showing better survival rates than males. Recently, metabolic shift and mitochondrial dysfunction have been demonstrated failure secondary to . In light evidence that estrogen protects function biogenesis noncardiovascular systems, we hypothesized the mechanism by which preserves via protection content oxidative capacity We used a well‐established model (Sugen+Hypoxia)...
GEnome-scale Network REconstructions (GENREs) mathematically describe metabolic reactions of an organism or a specific cell type. GENREs can be used with number constraint-based reconstruction and analysis (COBRA) methods to make computational predictions on how system changes in different environments. We created simplified GENRE (referred as iSIM) that captures central energy metabolism nine illustrate the use promote understanding methods. demonstrate simulation single double gene...
The enzyme fumarase catalyzes the reversible hydration of fumarate to malate. reaction catalyzed by is critical for cellular energetics as a part tricarboxylic acid cycle, which produces reducing equivalents drive oxidative ATP synthesis. A catalytic mechanism that can account kinetic behavior observed in both isotope exchange studies and initial velocity has not yet been identified. In present study, we develop an 11-state model based on current consensus its design series experiments...
During human heart failure, the balance of cardiac energy use switches from predominantly fatty acids (FAs) to glucose. We hypothesized that this substrate shift was result mitochondrial degeneration; therefore, we examined oxidation and ultrastructure in failing by using respirometry, transmission electron microscopy, gene expression studies demographically matched donor left ventricular (LV) tissues. Surprisingly, respiratory capacities for LV isolated mitochondria (n = 9) were not...
In diseased states, the heart can shift to use different carbon substrates, measured through changes in uptake of metabolites by imaging methods or blood metabolomics. However, it is not known whether these are a result transcriptional external factors. Here, we explore late-stage failure using publicly available data integrated with model metabolism. First, present heart-specific genome-scale metabolic network reconstruction (GENRE), iCardio. Next, demonstrate utility iCardio interpreting...
Abstract In order to provide timely treatment for organ damage initiated by therapeutic drugs or exposure environmental toxicants, we first need identify markers that an early diagnosis of potential adverse effects before permanent occurs. Specifically, the liver, as a primary prone toxicants-induced injuries, lacks diagnostic are specific and sensitive onset injury. Here, plasma metabolites toxicant-induced injury, used constraint-based modeling approach with genome-scale network...
Analysis of biochemical systems requires reliable and self-consistent databases thermodynamic properties for reactions. Here a database the reactions glycolysis tricarboxylic acid cycle is developed from measured equilibrium data. Species-level free energies formation are estimated on basis comparing model predictions reaction-level constants to previously reported data obtained under different experimental conditions. Matching involves applying state corrections ionic strength, pH, metal...
Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca(2+) under various substrate and ADP incubation conditions in an attempt determine understand the role of maintaining energy homeostasis working hearts. In this study, we tested hypothesis that, at physiological temperature 1 mM extramitochondrial free magnesium, can stimulate overall mitochondrial NAD(P)H generation flux rat heart mitochondria utilizing pyruvate malate as substrates both subsaturating...
Context-specific GEnome-scale metabolic Network REconstructions (GENREs) provide a means to understand cellular metabolism at deeper level of physiological detail. Here, we use transcriptomics data from chemically-exposed rat hepatocytes constrain GENRE hepatocyte and predict biomarkers liver toxicity using the Transcriptionally Inferred Metabolic Biomarker Response algorithm. We profiled alterations in following vitro exposure four toxicants (acetaminophen, carbon tetrachloride,...
The compulsory-ordered ternary catalytic mechanism for two-substrate two-product enzymes is analyzed to account binding of inhibitors each the four enzyme states and maintain relationship between kinetic constants reaction equilibrium constant. developed quasi-steady flux expression applied analysis data from citrate synthase determine parameterize a scheme in terms biochemical species, which effects pH, ionic strength, cation species are explicitly accounted data. This provides mechanistic...
Binding, lateral diffusion and exchange are fundamental dynamic processes involved in protein association with cellular membranes. In this study, we developed numerical simulations of fluorophores membranes arbitrary bleach geometry the membrane-localized fluorophore cytosol during fluorescence recovery after photobleaching (FRAP) experiments. The model were used to design FRAP experiments varying region sizes on plasma wild-type GFP-Ras2 a dual lipid anchor mutant GFP-Ras2C318S single live...