A systems perspective on placental amino acid transport.
A systems perspective on placental amino acid transport.
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DOI：
10.1113/jp274883
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Lewis RM
中科院分区：
文献类型：
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作者：
Cleal JK;Lofthouse EM;Sengers BG;Lewis RM
胎盘氨基酸转移是一个复杂的过程，对胎儿发育至关重要。氨基酸转运受损会导致胎儿生长受限，这可能会导致终生健康后果。氨基酸在胎盘合体滋养层细胞间的跨上皮转移需要顶端和基底膜上的蓄积、交换和促进转运蛋白协同工作。然而，转运体本身并不决定氨基酸的转运，而影响底物利用率的因素，如血流和代谢，也可能成为转运的限速因素。为了确定限速过程，有必要采取一种系统的方法，认识到这些过程的相互依存。新技术有可能向胎盘提供有针对性的干预，并帮助发育不良的胎儿。虽然许多因素是氨基酸转移所必需的，但新的治疗方法如果想要有效，就需要针对限速因素。这篇综述将概述决定氨基酸转移的因素，并描述它们是如何相互依赖的。它还将强调计算模型作为理解这一过程的工具的作用。
Placental amino acid transfer is a complex process that is essential for fetal development. Impaired amino acid transfer causes fetal growth restriction, which may have lifelong health consequences. Transepithelial transfer of amino acids across the placental syncytiotrophoblast requires accumulative, exchange and facilitated transporters on the apical and basal membranes to work in concert. However, transporters alone do not determine amino acid transfer and factors that affect substrate availability, such as blood flow and metabolism, may also become rate‐limiting for transfer. In order to determine the rate‐limiting processes, it is necessary to take a systems approach which recognises the interdependence of these processes. New technologies have the potential to deliver targeted interventions to the placenta and help poorly growing fetuses. While many factors are necessary for amino acid transfer, novel therapies need to target the rate‐limiting factors if they are going to be effective. This review will outline the factors which determine amino acid transfer and describe how they become interdependent. It will also highlight the role of computational modelling as a tool to understand this process.