L-serine uptake by human placental microvillous membrane vesicles.
The human fetus requires more glycine than any other amino acid but placental glycine transfer to the fetus is insufficient to meet fetal demand. L-Serine could represent a major metabolic source of glycine for the human fetus but little is known about the kinetics and physiology of L-serine uptake by the human placenta. We have characterised the amino acid transport systems involved in the uptake of L-serine by the microvillous membrane of the human placental syncytiotrophoblast and compared the uptake rates to those of glycine. L-Serine uptake into microvillous membrane (MVM) vesicles was primarily mediated by system A (MeAIB inhibitable) and system L (BCH inhibitable). Further characterisation using specific substrates of LAT1 and LAT2 found the pattern of L-serine uptake was consistent with that expected for uptake mediated by LAT2. Uptakes were performed with tracer levels of (14)C-L-serine, physiological levels of L-serine, or with physiological levels of amino acids. As amino acid concentrations rose, the proportion of uptake by System L decreased while uptake by uncharacterised Na(+)-independent systems increased. Uptake of Lserine into MVM vesicles had a V(max) of 2.1+/-0.4 nmol/mg protein/min, which was significantly higher than for glycine (V(max) 1.0+/-0.2 nmol/mg protein/min). This indicates that MVM vesicles have a higher uptake capacity for L-serine than glycine, despite a greater demand for glycine over serine for fetal protein synthesis. Further studies are now required to define the fate of L-serine taken up by the placenta and its importance for the fetus.
Lewis
R M
RM
Centre for Developmental Origins of Health and Disease, University of Southampton, Level F MP887, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK. rml2@soton.ac.uk <rml2@soton.ac.uk>
Glazier
J
J
Greenwood
S L
SL
Bennett
E J
EJ
Godfrey
K M
KM
Jackson
A A
AA
Sibley
C P
CP
Cameron
I T
IT
Hanson
M A
MA
D026924:Amino Acid Transport System A / Q000235:genetics; D027182:Amino Acid Transport System y+ / Q000235:genetics; D027241:Amino Acid Transport System y+L / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics; D006801:Humans; D008871:Microvilli / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012694:Serine / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000235:genetics
D026924:Amino Acid Transport System A; D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D027301:Fusion Regulatory Protein 1, Light Chains; D009363:Neoplasm Proteins; C445761:SLC38A1 protein, human; C498797:SLC38A2 protein, human; C101832:SLC38A3 protein, human; C115131:SLC43A1 protein, human; C420862:SLC7A4 protein, human; C420646:SLC7A8 protein, human; D019831:Sodium-Calcium Exchanger; D012694:Serine