Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation.
Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation.
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DOI：
10.1152/ajpregu.00405.2015
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发表时间：
2016-02-01
期刊：
影响因子：
--
通讯作者：
Lewis RM
中科院分区：
文献类型：
--
作者：
Lofthouse EM;Perazzolo S;Brooks S;Crocker IP;Glazier JD;Johnstone ED;Panitchob N;Sibley CP;Widdows KL;Sengers BG;Lewis RM
膜转运蛋白被认为对胎盘氨基酸转移至关重要，但血流和代谢等其他因素的贡献却知之甚少。在这项研究中，我们结合联合收割机的实验和建模方法，以了解[14 C]苯丙氨酸转移的决定因素，通过离体灌注人胎盘。[14 C]苯丙氨酸通过离体灌注人胎盘的转移测定在不同的母亲和胎儿流量。母体流速分别设定为10、14和18 ml/min，持续1 h。在每个母体流速下，将胎儿流速设定为3、6和9 ml/min，各持续20 min。[14 C]苯丙氨酸的出现在母体和胎儿静脉渗出液中进行测量。苯丙氨酸转移的计算建模进行，以允许比较的实验数据与预测的苯丙氨酸的吸收和转移在不同的初始假设。[14 C]苯丙氨酸的胎盘摄取（mol/min）随母体流量而增加，但不随胎儿流量而增加。[14 C]苯丙氨酸向胎儿循环的输送（mol/min）与胎儿或母体血流无关。胎盘苯丙氨酸摄取和苯丙氨酸到胎儿循环的净流量之间没有关系，这表明流量或转运蛋白介导的摄取以外的因素是苯丙氨酸转移的重要决定因素。这些观察结果可以通过胎盘内游离氨基酸水平的严格调节或介导苯丙氨酸转运的易化转运蛋白的性质来解释。我们认为，氨基酸代谢，主要是纳入蛋白质，控制游离氨基酸水平，因此，胎盘转移。
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 [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]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 [14C]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 [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]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.
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影响因子：
2.7
作者：
Sengers, B. G.;Please, C. P.;Lewis, R. M.
通讯作者：
Lewis, R. M.
影响因子：
3.8
作者：
Schneider, H;Reiber, W;Malek, A
通讯作者：
Malek, A
影响因子：
9
作者：
通讯作者：
--
影响因子：
2.1
作者：
BERSINGER, NA;MALEK, A;SCHNEIDER, H
通讯作者：
SCHNEIDER, H
影响因子：
3.8
作者：
Lewis, R. M.;Glazier, J.;Hanson, M. A.
通讯作者：
Hanson, M. A.