Computational modelling of amino acid transfer interactions in the placenta
Computational modelling of amino acid transfer interactions in the placenta
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DOI：
10.1113/expphysiol.2010.052902
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发表时间：
2010-07-01
影响因子：
2.7
通讯作者：
Lewis, R. M.
中科院分区：
文献类型：
--
作者：
Sengers, B. G.;Please, C. P.;Lewis, R. M.
通过胎盘从母体向胎儿的氨基酸转移在正常发育中起着关键作用，而限制性转移与胎儿生长受限有关。胎盘氨基酸转运涉及15个或更多个转运蛋白和20个氨基酸的相互作用。这种复杂性意味着知道哪些转运蛋白存在并不足以预测它们如何作为一个系统一起运作。因此，为了研究胎盘氨基酸转运如何作为一个系统发生，开发了一个综合的数学/计算建模框架来表示多种氨基酸的同时转运。该方法是基于一个房室模型，其中单独的母体，合胞体滋养层和胎儿的体积进行了区分，和运输建模的母体和胎儿的合胞体滋养层膜使用Michaelis-Menten型动力学。将该模型与研究丝氨酸-丙氨酸交换的胎盘灌流实验进行比较，发现其对应良好。研究结果表明，不同的转运体如何作为一个综合系统协同工作，并评估它们的相对重要性。胎盘胎儿丝氨酸交换被认为是最敏感的基底膜转运蛋白的特点，但一系列的次要，不太直观的影响也被发现。虽然这项工作只解决了一个相对简单的三个氨基酸系统，它证明了该方法的可行性，并可以扩展到纳入其他实验参数。最终，这种方法将允许氨基酸转移的生理模拟。这将增强我们对这些复杂系统和胎盘在健康和疾病中的功能的理解。
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 three 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.