Computational modelling of amino acid transfer interactions in the placenta
Computational modelling of amino acid transfer interactions in the placenta
Amino acid transfer from mother to fetus via the placenta plays a critical role in normal development, and restricted transfer is associated with fetal growth restriction. Placental amino acid transfer involves the interaction of 15 or more transporters and 20 amino acids. This complexity means that knowing which transporters are present is not sufficient to predict how they operate together as a system. Therefore, in order to investigate how placental amino acid transfer occurs as a system an integrated mathematical/computational modelling framework was developed to represent the simultaneous transport of multiple amino acids. The approach was based on a compartmental model, in which separate maternal, syncytiotrophoblast and fetal volumes were distinguished, and transporters were modelled on the maternal and fetal facing membranes of the syncytiotrophoblast using Michaelis-Menten type kinetics. The model was tested in comparison with placental perfusion experiments studying serine-alanine exchange and found to correspond well. The results demonstrated how the different transporters can work together as an integrated system and allowed their relative importance to be assessed. Placental/fetal serine exchange was found to be most sensitive to basal membrane transporter characteristics, but a range of secondary less intuitive effects were also revealed. While this work only addressed a relatively simple 3 amino acid system it demonstrates the feasibility of the approach and could be extended to incorporate additional experimental parameters. Ultimately this approach will allow physiological simulations of amino acid transfer. This will enhance our understanding of these complex systems and placental function in health and disease.
829-840
Sengers, Bram G.
d6b771b1-4ede-48c5-9644-fa86503941aa
Please, Colin P.
118dffe7-4b38-4787-a972-9feec535839e
Lewis, Rohan M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
23 April 2010
Sengers, Bram G.
d6b771b1-4ede-48c5-9644-fa86503941aa
Please, Colin P.
118dffe7-4b38-4787-a972-9feec535839e
Lewis, Rohan M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Sengers, Bram G., Please, Colin P. and Lewis, Rohan M.
(2010)
Computational modelling of amino acid transfer interactions in the placenta.
Experimental Physiology, 95 (7), .
(doi:10.1113/expphysiol.2010.052902).
Abstract
Amino acid transfer from mother to fetus via the placenta plays a critical role in normal development, and restricted transfer is associated with fetal growth restriction. Placental amino acid transfer involves the interaction of 15 or more transporters and 20 amino acids. This complexity means that knowing which transporters are present is not sufficient to predict how they operate together as a system. Therefore, in order to investigate how placental amino acid transfer occurs as a system an integrated mathematical/computational modelling framework was developed to represent the simultaneous transport of multiple amino acids. The approach was based on a compartmental model, in which separate maternal, syncytiotrophoblast and fetal volumes were distinguished, and transporters were modelled on the maternal and fetal facing membranes of the syncytiotrophoblast using Michaelis-Menten type kinetics. The model was tested in comparison with placental perfusion experiments studying serine-alanine exchange and found to correspond well. The results demonstrated how the different transporters can work together as an integrated system and allowed their relative importance to be assessed. Placental/fetal serine exchange was found to be most sensitive to basal membrane transporter characteristics, but a range of secondary less intuitive effects were also revealed. While this work only addressed a relatively simple 3 amino acid system it demonstrates the feasibility of the approach and could be extended to incorporate additional experimental parameters. Ultimately this approach will allow physiological simulations of amino acid transfer. This will enhance our understanding of these complex systems and placental function in health and disease.
This record has no associated files available for download.
More information
Published date: 23 April 2010
Organisations:
Dev Origins of Health & Disease, Bioengineering Sciences, Applied Mathematics
Identifiers
Local EPrints ID: 149491
URI: http://eprints.soton.ac.uk/id/eprint/149491
ISSN: 0958-0670
PURE UUID: 0361ba77-6432-46a9-9313-d199e241edcf
Catalogue record
Date deposited: 30 Apr 2010 11:14
Last modified: 14 Mar 2024 02:51
Export record
Altmetrics
Contributors
Author:
Colin P. Please
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
