Bar-Code Computers Ltd., POB 2013, 3912001, Tirat-Carmel, Israel.
J Membr Biol. 2019 Dec;252(6):617-626. doi: 10.1007/s00232-019-00097-y. Epub 2019 Sep 25.
The high demand of the fetus for Docosahexaenoic acid, DHA, is satisfied by a concert of several mechanisms that take place in the placental terminal villi. Scarcity of laboratory data makes the detailed description of these mechanisms elusive. Here, the DHA transport across the placenta is modeled as a boundary value problem that accounts for diffusion, reactions with fatty acids binding proteins, FABPs, and metabolic consumption within the Syncytiotrophoblast, ST. For any given DHA fluxes at the bordering membranes, analytical and numerical solutions yield the DHA concentration profile within the ST. We find that in order to comply with adequate DHA delivery to the fetus and with physiological DHA concentrations in the maternal and fetal circulations, it is essential to have a significant rise of DHA concentration at the microvillus membrane, MVM and a rapid dissociation of the DHA from the FABP. The model establishes the relations between the concentrations of the FABPs in the ST, their equilibrium dissociation constant from the DHA, and the placental DHA metabolic degradation rate, hitherto unknown. We conclude that the bound (to the protein) DHA molecule is degraded at a rate of 0.3-0.45 s.
胎儿对二十二碳六烯酸(DHA)的高需求是通过胎盘终末绒毛中发生的几个机制共同满足的。由于实验室数据的匮乏,这些机制的详细描述难以捉摸。在这里,将 DHA 通过胎盘的转运建模为一个边值问题,该问题考虑了扩散、与脂肪酸结合蛋白(FABP)的反应以及合体滋养层(ST)内的代谢消耗。对于边界膜上的任何给定的 DHA 通量,分析和数值解都会得出 ST 内的 DHA 浓度分布。我们发现,为了向胎儿提供足够的 DHA 输送,并保持母体和胎儿循环中的生理 DHA 浓度,在微绒毛膜(MVM)处 DHA 浓度必须显著升高,并且 DHA 必须从 FABP 中快速解离。该模型建立了 ST 中 FABP 的浓度与其与 DHA 的平衡解离常数以及胎盘 DHA 代谢降解率之间的关系,这些关系迄今为止尚不清楚。我们得出的结论是,结合(与蛋白质结合)的 DHA 分子以 0.3-0.45 s 的速率降解。