title: Partial characterization of folate uptake in microvillous membrane vesicles isolated from human placenta.
abstract: The purpose of the present study was to determine biochemical parameters of folate uptake, and the putative contribution of the membrane-anchored folate receptor in microvillous membrane vesicles obtained from the syncytiotrophoblast of human term placenta. Uptake of [3H]-pteroylglutamic acid (PGA) by microvillous membrane vesicles was pH dependent with a maximum at pH 6.0, and attained equilibrium at 60 min of incubation. Uptake was higher in the presence on an inward pH gradient (pHout = 6.0; pHin = 7.5) than in the absence of the gradient (pHout = pHin = 6.0). The effect of changes in medium osmolality showed that both binding to the vesicular membrane and internalization contributed to the measured [3H]-PGA uptake. Equilibrium uptake experiments using [3H]-PGA concentrations within the physiological range of folate in blood serum showed that saturation was achieved at 30 nM and revealed a single class of binding sites with a Kd of 1.8 nM for [3H]-PGA. Cleavage of the glycosyl-phosphatidylinositol moiety of the folate receptor, which anchors the receptor to the membrane, with phosphatidylinositol-specific phospholipase C resulted in a reduction of about 80% in [3H]-PGA uptake. In conclusion, our results showed that the folate uptake in the maternally facing membrane of the human placenta presents a saturable component and is mediated by the folate receptor to ensure an adequate maternal-fetal folate transfer.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Brasil.
authors.forename: C
authors.initials: C
authors.lastname: Henriques
authors.forename: N M
authors.initials: NM
authors.lastname: Trugo
mesh_terms: D002352:Carrier Proteins / Q000502:physiology; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000493:pharmacokinetics*; D006801:Humans; D008871:Microvilli / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000648:ultrastructure*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid