L-serine uptake by human placental microvillous membrane vesicles

L-serine uptake by human placental microvillous membrane vesicles
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DOI:
10.1016/j.placenta.2006.06.014
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发表时间:
2007-05-01
期刊:
影响因子:
3.8
通讯作者:
Hanson, M. A.
Hanson, M. A.
中科院分区:
医学3区
文献类型:
--
作者:
Lewis, R. M.;Glazier, J.;Hanson, M. A.

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人类胎儿对甘氨酸的需求比任何其他氨基酸都多,但胎盘转移给胎儿的甘氨酸不足以满足胎儿的需求。L-丝氨酸可能是人类胎儿甘氨酸的主要代谢来源,但对人类胎盘摄取L-丝氨酸的动力学和生理学知之甚少。我们的特点是参与摄取L-丝氨酸的人胎盘合胞滋养层的微绒毛膜的氨基酸转运系统和比较的摄取率的glycine. L-丝氨酸摄取到微绒毛膜(MVM)囊泡主要介导的系统A(MeAIB可吸收)和系统L(BCH可吸收)。使用LAT 1和LAT 2的特异性底物的进一步表征发现L-丝氨酸摄取的模式与预期的由LAT 2介导的摄取一致。用示踪剂水平的C-14-L-丝氨酸、生理水平的L-丝氨酸或生理水平的氨基酸进行摄取。随着氨基酸浓度的升高,系统L的摄取比例降低,而非Na+依赖性系统的摄取增加。MVM囊泡对L-丝氨酸的摄取具有2.1 +/- 0.4 nmol/mg蛋白/min的V-max,这显著高于甘氨酸(V-max 1.0 +/- 0.2 nmol/mg蛋白/min)。这表明MVM囊泡对L-丝氨酸的摄取能力高于甘氨酸,尽管对于胎儿蛋白质合成,甘氨酸的需求高于丝氨酸。现在需要进一步的研究来确定胎盘摄取的L-丝氨酸的命运及其对胎儿的重要性。(c)2006爱思唯尔有限公司保留所有权利。
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 C-14-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 L-serine 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. (c) 2006 Elsevier Ltd. All rights reserved.