The University of Southampton
University of Southampton Institutional Repository

Computational modelling of placental amino acid transfer as an integrated system

Computational modelling of placental amino acid transfer as an integrated system
Computational modelling of placental amino acid transfer as an integrated system
Placental amino acid transfer is essential for fetal development and its impairment is associated with poor fetal growth. Amino acid transfer is mediated by a broad array of specific plasma membrane transporters with overlapping substrate specificity. However, it is not fully understood how these different transporters work together to mediate net flux across the placenta. Therefore the aim of this study was to develop a new computational model to describe how human placental amino acid transfer functions as an integrated system. Amino acid transfer from mother to fetus requires transport across the two plasma membranes of the placental syncytiotrophoblast, each of which contains a distinct complement of transporter proteins. A compartmental modelling approach was combined with a carrier based modelling framework to represent the kinetics of the individual accumulative, exchange and facilitative classes of transporters on each plasma membrane. The model successfully captured the principal features of transplacental transfer. Modelling results clearly demonstrate how modulating transporter activity and conditions such as phenylketonuria, can increase the transfer of certain groups of amino acids, but that this comes at the cost of decreasing the transfer of others, which has implications for developing clinical treatment options in the placenta and other transporting epithelia.
amino acids, placenta, epithelial transport, mathematical model
0304-4165
1-31
Panitchob, N.
84152342-d60f-457b-9bb9-6d734c094a4e
Widdows, K.L.
25faab47-b4fc-4837-99fb-fa6b0e15398e
Crocker, I.P.
b8686961-d199-4a28-bd16-bbf71821bd96
Johnstone, E.D.
354bf081-807b-4ca9-8956-7be1287f834c
Please, C.P.
48277c2e-c9eb-46f8-8995-1cf885922818
Sibley, C.P.
6e4ffcd0-f4b5-41c4-8360-9d78b9e9156c
Glazier, J.D.
db2aa1ae-5208-4a56-9213-4521128577e1
Lewis, R.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Sengers, B.
d6b771b1-4ede-48c5-9644-fa86503941aa
Panitchob, N.
84152342-d60f-457b-9bb9-6d734c094a4e
Widdows, K.L.
25faab47-b4fc-4837-99fb-fa6b0e15398e
Crocker, I.P.
b8686961-d199-4a28-bd16-bbf71821bd96
Johnstone, E.D.
354bf081-807b-4ca9-8956-7be1287f834c
Please, C.P.
48277c2e-c9eb-46f8-8995-1cf885922818
Sibley, C.P.
6e4ffcd0-f4b5-41c4-8360-9d78b9e9156c
Glazier, J.D.
db2aa1ae-5208-4a56-9213-4521128577e1
Lewis, R.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Sengers, B.
d6b771b1-4ede-48c5-9644-fa86503941aa

Panitchob, N., Widdows, K.L., Crocker, I.P., Johnstone, E.D., Please, C.P., Sibley, C.P., Glazier, J.D., Lewis, R. and Sengers, B. (2016) Computational modelling of placental amino acid transfer as an integrated system. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1-31. (doi:10.1016/j.bbamem.2016.03.028). (PMID:27045077)

Record type: Article

Abstract

Placental amino acid transfer is essential for fetal development and its impairment is associated with poor fetal growth. Amino acid transfer is mediated by a broad array of specific plasma membrane transporters with overlapping substrate specificity. However, it is not fully understood how these different transporters work together to mediate net flux across the placenta. Therefore the aim of this study was to develop a new computational model to describe how human placental amino acid transfer functions as an integrated system. Amino acid transfer from mother to fetus requires transport across the two plasma membranes of the placental syncytiotrophoblast, each of which contains a distinct complement of transporter proteins. A compartmental modelling approach was combined with a carrier based modelling framework to represent the kinetics of the individual accumulative, exchange and facilitative classes of transporters on each plasma membrane. The model successfully captured the principal features of transplacental transfer. Modelling results clearly demonstrate how modulating transporter activity and conditions such as phenylketonuria, can increase the transfer of certain groups of amino acids, but that this comes at the cost of decreasing the transfer of others, which has implications for developing clinical treatment options in the placenta and other transporting epithelia.

Text
Panitchob 2016 - BBA Biomembranes - accepted.pdf - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 31 March 2016
e-pub ahead of print date: 2 April 2016
Keywords: amino acids, placenta, epithelial transport, mathematical model
Organisations: Faculty of Medicine, Bioengineering Group

Identifiers

Local EPrints ID: 390835
URI: http://eprints.soton.ac.uk/id/eprint/390835
ISSN: 0304-4165
PURE UUID: e610caa9-554e-46d0-848f-ac5eab1dd559
ORCID for R. Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for B. Sengers: ORCID iD orcid.org/0000-0001-5859-6984

Catalogue record

Date deposited: 07 Apr 2016 13:12
Last modified: 18 Feb 2021 17:07

Export record

Altmetrics

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

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×