Figure 1.

Experimental design for modeling system L amino acid transport across the MVM of human placenta. A) Schematic representation of the mode of system L amino acid transport across MVM comprising a capacity to function both as an obligate antiporter EX, as well as a facilitated transporter as defined by the carrier model. A^I and A^II represent tracer amino acid at the external face of MVM and in the cytoplasmic compartment of the SCT, respectively. B) The computational model was applied to describe the mixed transport carrier model with exchanger and facilitated transporter capacities as illustrated in A (19). For obligate exchange, transporter X can bind to either radiolabeled tracer amino acid A or an unlabeled amino acid B to form a complex AX^I or BX^I, respectively, which can translocate between the external facing aspect of MVM in direct contact with maternal blood (MB) to the inside face of MVM in contact with the cytoplasm of SCT, represented as AX^II or BX^II, respectively. In contrast, transporter X can also translocate between the external and internal faces unloaded, depending on the parameter h, which describes the rate at which the unbound transporter (X^I or X^II) can translocate back across the membrane relative to the rate of amino acid transporter binding (D). The case h = 0 corresponds to an obligatory exchanger, whereas for h > 0, the transporter will display unidirectional facilitative transport governed by the direction of the transmembrane amino acid concentration gradient. C) The computational model was tested experimentally by measuring the Na⁺-independent uptake of [¹⁴C]l-serine (A^I) (tracer) into isolated human placental MVM vesicles in response to various intravesicular (B^II) and extravesicular (B^I) additions of unlabeled l-serine (Ci) outlined in the experimental matrix in Cii. CT, cytotrophoblast cell; EX/FT, exchanger/facilitated transporter.