title: Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation.
abstract: Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [(14)C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [(14)C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [(14)C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer.
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: E M
authors.initials: EM
authors.lastname: Lofthouse
authors.affiliation: Bioengineering Science Research Group, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom;
authors.forename: S
authors.initials: S
authors.lastname: Perazzolo
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, United Kingdom;
authors.forename: S
authors.initials: S
authors.lastname: Brooks
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, and St. Mary's Hospital and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; and.
authors.forename: I P
authors.initials: IP
authors.lastname: Crocker
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, and St. Mary's Hospital and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; and.
authors.forename: J D
authors.initials: JD
authors.lastname: Glazier
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, and St. Mary's Hospital and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; and.
authors.forename: E D
authors.initials: ED
authors.lastname: Johnstone
authors.affiliation: Bioengineering Science Research Group, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom;
authors.forename: N
authors.initials: N
authors.lastname: Panitchob
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, and St. Mary's Hospital and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; and.
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, and St. Mary's Hospital and Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; and.
authors.forename: K L
authors.initials: KL
authors.lastname: Widdows
authors.affiliation: Bioengineering Science Research Group, Faculty of Engineering and the Environment, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: B G
authors.initials: BG
authors.lastname: Sengers
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Rohan.Lewis@soton.ac.uk.
authors.forename: R M
authors.identifier: 0000-0003-4044-9104
authors.initials: RM
authors.lastname: Lewis
mesh_terms: D001692:Biological Transport; D002250:Carbon Radioisotopes; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D010477:Perfusion; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism*; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy
chemical_list: D002250:Carbon Radioisotopes; D010649:Phenylalanine; D003404:Creatinine
keywords: amino acid transfer; blood flow; exchanger; facilitated transport; metabolism