Long-chain fatty acids (FAs) are important substrates used by the heart to fulfil its energy requirements. Prior to mitochondrial oxidation, blood-borne FAs must pass through the cell membrane of the cardiac myocyte (sarcolemma). The mechanism underlying the sarcolemmal transport of FAs is incompletely understood. The aim of the present study was to estimate the trans-sarcolemmal FA uptake rate using a comprehensive computer model, in which the most relevant mechanisms proposed for cardiac FA uptake were incorporated. Our in silico findings show that diffusion of FA, present in its unbound form (uFA) in close proximity to the outer leaflet of the sarcolemma and serving as sole FA source, is insufficient to account for the physiological FA uptake rate. The inclusion of a hypothetical membrane-associated FA-TFPC (FA-transport-facilitating protein complex) in the model calculations substantially increased the FA uptake rate across the sarcolemma. The model requires that the biological properties of the FA-TFPC allow for increasing the rate of absorption of FA into the outer leaflet and the ‘flip-flop’ rate of FA from the outer to the inner leaflet of the sarcolemma. Experimental studies have identified various sarcolemma-associated proteins promoting cardiac FA uptake. It remains to be established whether these proteins possess the properties predicted by our model. Our findings also indicate that albumin receptors located on the outer leaflet of the sarcolemma facilitate the transfer of FA across the membrane to a significant extent. The outcomes of the computer simulations were verified with physiologically relevant FA uptake rates as assessed in the intact, beating heart in experimental studies.
Skip Nav Destination
Article navigation
February 2006
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
January 13 2006
Computational evidence for protein-mediated fatty acid transport across the sarcolemma
Mark W. J. M. Musters;
Mark W. J. M. Musters
*Department of Electrical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
Search for other works by this author on:
James B. Bassingthwaighte;
James B. Bassingthwaighte
†Department of Bioengineering, University of Washington, Seattle, WA 98195-7962, U.S.A.
Search for other works by this author on:
Natal A. W. van Riel;
Natal A. W. van Riel
‡Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
Search for other works by this author on:
Ger J. van der Vusse
Ger J. van der Vusse
1
§Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands
1To whom correspondence should be addressed (email vandervusse@fys.unimaas.nl).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 27 2005
Revision Received:
October 04 2005
Accepted:
October 06 2005
Accepted Manuscript online:
October 06 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 393 (3): 669–678.
Article history
Received:
May 27 2005
Revision Received:
October 04 2005
Accepted:
October 06 2005
Accepted Manuscript online:
October 06 2005
Citation
Mark W. J. M. Musters, James B. Bassingthwaighte, Natal A. W. van Riel, Ger J. van der Vusse; Computational evidence for protein-mediated fatty acid transport across the sarcolemma. Biochem J 1 February 2006; 393 (3): 669–678. doi: https://doi.org/10.1042/BJ20050869
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.