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Homocysteine transport by systems L, A and y + L across the microvillous plasma membrane of human placenta
Author(s) -
Tsitsiou Eleni,
Sibley Colin P.,
D'Souza Stephen W.,
Catanescu Otilia,
Jacobsen Donald W.,
Glazier Jocelyn D.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.173393
Subject(s) - chemistry , homocysteine , placenta , biochemistry , membrane transport , medicine , fetus , endocrinology , membrane , biology , pregnancy , genetics
Elevated maternal plasma levels of homocysteine (Hcy) are associated with pregnancy complications and adverse neonatal outcomes, suggesting placental transport of Hcy may impact on fetal development. However, such transport mechanisms have not been defined. In this study we characterise Hcy transport mechanisms across the microvillous plasma membrane (MVM) of the syncytiotrophoblast, the transporting epithelium of human placenta. Three candidate transport systems, systems L, A and y + L, were examined utilising competitive inhibition to investigate the effects of Hcy on the uptake of well‐characterised radiolabelled substrates for each system into isolated MVM vesicles, and that of model substrates on 10 μ m [ 35 S] l –Hcy uptake. System L activity was inhibited by both l ‐Hcy and dl –Hcy, comparable to model substrates including 2–aminobicyclo[2.2.1]heptane‐2‐carboxylic acid (BCH). System L constituted the major transport mechanism, with significant BCH inhibition (∼69%) of [ 35 S] l –Hcy uptake. System A activity was also inhibited by l –Hcy and dl ‐Hcy with a smaller contribution (∼21%) to [ 35 S] l –Hcy uptake. Inhibition by l –Hcy and dl –Hcy of system y + L activity was Na + sensitive with a significant inhibition constant ( K i ) shift observed following K + replacement; l –arginine reduced [ 35 S] l –Hcy uptake by ∼19%. Kinetic modelling of [ 35 S] l –Hcy uptake resolved two, Na + ‐independent, transport components ( K m 72 μ m and 9.7 m m ). This study provides evidence for the involvement of systems L, A and y + L in placental Hcy transport. Such transport, by competing with endogenous amino acids for transporter activity, could have major implications for syncytiotrophoblast metabolism and function as well as fetal development.