Faculty of Medicine, University of Southampton, Southampton, UK.
Institute of Life Sciences, University of Southampton, Southampton, UK.
J Physiol. 2018 Dec;596(23):5511-5522. doi: 10.1113/JP274883. Epub 2018 Sep 7.
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.
胎盘氨基酸转运是一个复杂的过程,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,这可能会对其一生的健康产生影响。氨基酸穿过胎盘合体滋养层的跨上皮转运需要在顶膜和基底膜上有累积、交换和易化转运体协同工作。然而,转运体本身并不能决定氨基酸的转运,并且可能会影响底物可用性的因素,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,有必要采用一种系统的方法,认识到这些过程的相互依存性。新技术有可能将靶向干预措施递送到胎盘,并帮助生长不良的胎儿。虽然氨基酸转运需要许多因素,但如果新疗法要有效,就需要针对限速因素。这篇综述将概述决定氨基酸转运的因素,并描述它们是如何相互依赖的。它还将强调计算建模作为理解这一过程的工具的作用。