title: Computational modelling of placental amino acid transfer as an integrated system.
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.
authors.affiliation: Bioengineering Science Research Group, Faculty of Engineering and the Environment, University of Southampton, UK.
authors.forename: N
authors.initials: N
authors.lastname: Panitchob
authors.affiliation: Maternal & Fetal Health Research Centre, Institute of Human Development, University of Manchester, UK; St. Mary's Hospital & Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Widdows
authors.affiliation: Maternal & Fetal Health Research Centre, Institute of Human Development, University of Manchester, UK; St. Mary's Hospital & Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
authors.forename: I P
authors.initials: IP
authors.lastname: Crocker
authors.affiliation: Maternal & Fetal Health Research Centre, Institute of Human Development, University of Manchester, UK; St. Mary's Hospital & Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
authors.forename: E D
authors.initials: ED
authors.lastname: Johnstone
authors.affiliation: Mathematical Institute, Oxford University, Oxford, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Please
authors.affiliation: Maternal & Fetal Health Research Centre, Institute of Human Development, University of Manchester, UK; St. Mary's Hospital & Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
authors.affiliation: Maternal & Fetal Health Research Centre, Institute of Human Development, University of Manchester, UK; St. Mary's Hospital & Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Glazier
authors.affiliation: Faculty of Medicine, University of Southampton, UK; Institute for Life Sciences, University of Southampton, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Lewis
authors.affiliation: Bioengineering Science Research Group, Faculty of Engineering and the Environment, University of Southampton, UK; Institute for Life Sciences, University of Southampton, UK. Electronic address: B.G.Sengers@soton.ac.uk.
authors.forename: B G
authors.initials: BG
authors.lastname: Sengers
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D001692:Biological Transport; D003198:Computer Simulation; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000145:classification / Q000378:metabolism*; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014469:Umbilical Arteries / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D000596:Amino Acids; D026901:Membrane Transport Proteins
keywords: Amino acids; Epithelial transport; Mathematical model; Placenta