title: Homocysteine is transported by the microvillous plasma membrane of human placenta.
abstract: 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.
authors.affiliation: 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.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tsitsiou
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sibley
authors.forename: Stephen W
authors.initials: SW
authors.lastname: D'Souza
authors.forename: Otilia
authors.initials: O
authors.lastname: Catanescu
authors.forename: Donald W
authors.initials: DW
authors.lastname: Jacobsen
authors.forename: Jocelyn D
authors.initials: JD
authors.lastname: Glazier
mesh_terms: D026924:Amino Acid Transport System A / Q000378:metabolism / Q000502:physiology; D027062:Amino Acid Transport System L / Q000378:metabolism / Q000502:physiology; D027241:Amino Acid Transport System y+L / Q000378:metabolism / Q000502:physiology; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D006710:Homocysteine / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008871:Microvilli / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D013462:Sulfur Radioisotopes / Q000493:pharmacokinetics
chemical_list: D026924:Amino Acid Transport System A; D027062:Amino Acid Transport System L; D027241:Amino Acid Transport System y+L; D013462:Sulfur Radioisotopes; D006710:Homocysteine