title: L-serine uptake by human placental microvillous membrane vesicles.
abstract: 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.
authors.affiliation: 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>
authors.forename: R M
authors.initials: RM
authors.lastname: Lewis
authors.forename: J
authors.initials: J
authors.lastname: Glazier
authors.forename: S L
authors.initials: SL
authors.lastname: Greenwood
authors.forename: E J
authors.initials: EJ
authors.lastname: Bennett
authors.forename: K M
authors.initials: KM
authors.lastname: Godfrey
authors.forename: A A
authors.initials: AA
authors.lastname: Jackson
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
authors.forename: I T
authors.initials: IT
authors.lastname: Cameron
authors.forename: M A
authors.initials: MA
authors.lastname: Hanson
mesh_terms: 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
chemical_list: 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