Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C142
The metabolism of amino acids in the isolated human placenta
P. E. Day1, J. M. Jackson1, J. K. Cleal1, M. A. Hanson1, A. A. Jackson1, R. M. Lewis1
1. DOHaD, Southampton university, Southampton, United Kingdom.
Amino acid supply to the fetus depends on placental amino acid transport and metabolism. In sheep there is a glutamate-glutamine cycle between the placenta and the fetal liver. Fetal glutamate is taken up by the placenta and it is converted to glutamine, which is transported back to the fetus. The sheep placenta also utilizes amino nitrogen from maternal leucine to produce glutamate and subsequently glutamine. The aim of this study was to investigate the metabolism of fetal glutamate and maternal leucine in the human placenta. Placentas were collected immediately after delivery from normal term pregnancies, with approval from the local research ethics committee. 200 µmol/L 15N-glutamate was perfused into the fetal arterial circulation of the isolated human placental cotyledon for 5 hours. In separate experiments, 146 µmol/l 15N-leucine was perfused into the maternal arterial circulation of the isolated human placental cotyledon for 5 hours. In the fetal umbilical venous perfusates the transfer of 15N from glutamate or leucine to other amino acids was determined by Gas Chromatography-Mass Spectrometry and the concentrations of amino acids were measured by High Performance Liquid Chromatography. T tests were used to compare 15N enrichments to baseline. During fetal arterial perfusion of 15N-glutamate there was enrichment of glutamine, aspartate, isoleucine, proline, leucine and alanine in the fetal umbilical vein (n = 3, p < 0.05). The concentrations (mean ± SD μmol/L) of 15N enriched amino acids in the fetal umbilical venous perfusates were: glutamine 2.7±0.6, aspartate 1.3±0.37, alanine 0.23±0.04, leucine 0.23±0.06 and isoleucine 0.18±0.03. During maternal arterial 15N-leucine perfusion there was enrichment of glutamine, glutamate, aspartate, isoleucine, alanine and proline in the fetal umbilical vein (n = 4, p < 0.05). Concentrations (mean ± SD μmol/L) of 15N labelled amino acids in the fetal umbilical venous perfusates were: glutamine 1.04±0.32, glutamate 0.12± 0.07 and alanine 0.16±0.04. This data suggests that as in sheep, the human placenta utilizes fetal glutamate and maternal leucine to produce other amino acids, especially glutamine and aspartate. The appearance of glutamate derived 15N label in glutamine is consistent with glutamate-glutamine cycling but further experiments are required to exclude an aminotransferase exchange mechanism. As glutamine is essential for fetal growth the human placenta may synthesise glutamine to meet fetal metabolic requirements.
Where applicable, experiments conform with Society ethical requirements