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CAPILLARY‐TISSUE EXCHANGE OF SUBSTRATES AND NUCLEOSIDES IN CARDIAC ENERGETICS MODELING
Author(s) -
Bassingthwaighte James,
Jardine Bartholomew,
Raymond Gary
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1043.11
Subject(s) - chemistry , oxidative phosphorylation , glycolysis , myoglobin , biophysics , oxygen transport , hemoglobin , kinetics , metabolism , biochemistry , oxygen , biology , organic chemistry , physics , quantum mechanics
Modeling cardiac energetics involves all of the elements of supply or demand. It is complicated: the exchange processes are distributed in space, heterogeneous, requiring parallel units interacting with each other. Multicomponent, multiscale models for the analysis of data are complicated. Using modular units aids building and maintenance. A convenient module is one in which the number of connecting variables is minimized, and the internal complexity is isolated. The differential equation modeling platform JSim is designed for model‐based analysis of data using behavioral and sensitivity analysis, automated data fitting, and MonteCarlo for uncertainty quantification. For O2, CO2, substrates, and metabolites we constructed first a multisolute single capillary‐tissue unit with RBC, plasma, endothelial cells, interstitial space, and cardiomyocytes, ignoring other cell types. The substrates were O2, glucose, and palmitate; the processes were uptake, binding and buffering, and metabolism. Oxygen, binding to hemoglobin, has capillary gradients influenced by CO2, pH, ºC and 2,3‐DPG, requiring partial differential equations. Myoglobin facilitates cytosolic diffusion and buffering. For glucose, there is glycolysis, the pentose shunt, and buffering as glycogen. For palmitate, storage buffering as acyl‐CoA and di‐ and tri‐glyceride feed into beta‐oxidation and the Krebs cycle. Oxidative phosphorylation produces ATP used in muscle filament activation, ion pumps, and cell maintenance. Version 1 uses first order reactions. Mechanistic kinetics with thermodynamic constraints come with substituting high fidelity modules. (NIH grants R01‐EB8407; P50‐GM 094503)