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Mathematical Models Suggest Facilitated Fatty Acids Crossing of the Luminal Membrane in the Cardiac Muscle
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文摘
Long-chain fatty acids cross a few membranes on their way from the capillary blood to the cardiomyocyte cytosol, where they are utilized as an essential source of energy. Details of the transport mechanism across those membranes remained elusive despite decades of laboratory and theoretical work. Here we inspect several optional scenarios for the crossing of the luminal membrane of the endothelial cell, the first barrier that should be crossed: a passive diffusion, facilitation by receptors for albumin and facilitation by fatty acids transporters. Related measured rate constants are incorporated in a theoretical simulation that is based on reaction–diffusion equations. Asymptotic analytical solutions for the resulting stiff boundary value problems are formulated based on singular perturbations theory. We conclude that a passive diffusion has to be supplemented with facilitation mechanisms in order to meet energy requirements. Binding sites for albumin, scattered on the membrane face, might enhance the flux provided that they internalize the captured fatty acids and speed up the dissociation of the albumin-fatty acids complex. As such enhancement is moderate, another mechanism seems to be essential for an adequate supply of fatty acids. Lack of experimental data prohibits us from computing the quantitative effect of membrane fatty acids transporters but their involvement in the membrane crossing is inferred.

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