Maternal and Fetal Health Research Group, School of Biomedicine, University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, Oxford Road, Manchester, UK.
J Inherit Metab Dis. 2011 Feb;34(1):57-65. doi: 10.1007/s10545-010-9141-3. Epub 2010 Jun 22.
Elevated maternal plasma concentrations of homocysteine (Hcy) are associated with pregnancy complications and adverse neonatal outcomes. The postulate that we wish to advance here is that placental transport of Hcy, by competing with endogenous amino acids for transporter activity, may account for some of the damaging impacts of Hcy on placental metabolism and function as well as fetal development. In this article, we provide an overview of some recent studies characterising the transport mechanisms for Hcy across the microvillous plasma membrane (MVM) of the syncytiotrophoblast, the transporting epithelium of human placenta. Three Hcy transport systems have been identified, systems L, A and y(+)L. This was accomplished using a strategy of competitive inhibition to investigate the effects of Hcy on the uptake of well-characterised radiolabelled substrates for each transport system into isolated MVM vesicles. The reverse experiments were also performed, examining the effects of model substrates on [³⁵S]L-Hcy uptake. This article describes the evidence for systems L, A and y(+)L involvement in placental Hcy transport and discusses the physiological implications of these findings with respect to placental function and fetal development.
母体血浆中同型半胱氨酸（Hcy）水平升高与妊娠并发症和不良新生儿结局有关。我们在这里提出的假设是，Hcy 通过与内源性氨基酸竞争转运体活性进行胎盘转运，可能导致 Hcy 对胎盘代谢和功能以及胎儿发育产生一些损害影响。在本文中，我们概述了一些最近的研究，这些研究描述了 Hcy 通过合胞滋养层的微绒毛质膜（MVM）进行转运的机制，合胞滋养层是人类胎盘的转运上皮。已经鉴定出三种 Hcy 转运系统，即系统 L、A 和 y(+)L。这是通过竞争性抑制策略来研究 Hcy 对每个转运系统的已充分鉴定的放射性标记底物摄取的影响来实现的，将这些放射性标记底物加入到分离的 MVM 囊泡中。还进行了相反的实验，检查模型底物对 [³⁵S]L-Hcy 摄取的影响。本文描述了系统 L、A 和 y(+)L 参与胎盘 Hcy 转运的证据，并讨论了这些发现对胎盘功能和胎儿发育的生理意义。
