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Glutamate–glutamine cycle and exchange in the placenta–fetus unit during late pregnancy

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Abstract

The present review focuses on the physiological functions of glutamate–glutamine exchange involving placental amino acid transport and umbilical amino acid uptake in mammals (particularly in sows), with special emphasis on the associated regulating mechanisms. Glutamate plus glutamine are among the most abundant and the most utilized amino acids in fetus during late gestation. During pregnancy, amino acids, notably as precursors of macromolecules including proteins and nucleotides are involved in fetal development and growth. Amino acid concentrations in fetus are generally higher than in the mother. Among amino acids, the transport and metabolism of glutamate and glutamine during fetal development exhibit characteristics that clearly emphasize the importance of the interaction between the placenta and the fetal liver. Glutamate is quite remarkable among amino acids, which originate from the placenta, and is cleared from fetal plasma. In addition, the flux of glutamate through the placenta from the fetal plasma is highly correlated with the umbilical glutamate delivery rate. Glutamine plays a central role in fetal carbon and nitrogen metabolism and exhibits one of the highest fetal/maternal plasma ratio among all amino acids in human and other mammals. Glutamate is taken up by placenta from the fetal circulation and then converted to glutamine before being released back into the fetal circulation. Works are required on the glutamate–glutamine metabolism during late pregnancy in physiological and pathophysiological situations since such works may help to improve fetal growth and development both in humans and other mammals. Indeed, glutamine supplementation appears to ameliorate fetal growth retardation in sows and reduces preweaning mortality of piglets.

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Abbreviations

BCAA:

Branched-chain amino acids

CoA:

Coenzyme A

CPS1:

Carbamyl phosphate synthetase 1

GDM:

Gestational diabetes

GS:

Glutamine synthetase

IUGR:

Intrauterine growth restriction

MSG:

Monosodium glutamate

NADPH:

Nicotinamide adenine dinucleotide phosphate

NAG:

N-acetylglutamate

NAGS:

NAG synthase

NCG:

N-carbamoylglutamate

GDH:

Glutamate dehydrogenase

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Acknowledgments

The writing of this review paper was jointly supported by grants from the NSFC (31110103909, 31101730), the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2012BAD39B00), Chinese Academy of Sciences and Knowledge Innovation Project (CXJQ120113-1, 2012B091100259), China Postdoctoral Science Foundation funded project (2014M552022). Francois Blachier is a visiting professor granted by the Chinese Academy of Sciences (Grant no 2013T2S0014).

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None of the authors have any conflict of interest to declare.

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Authors and Affiliations

  1. Hunan Engineering and Research Center of Animal and Poultry Science, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, 410125, Changsha, China

    Xin Wu, Chunyan Xie, Yuzhe Zhang & Yulong Yin

  2. College of Animal Science and Technology, Hunan Agricultural University, 410128, Changsha, Hunan, China

    Xin Wu, Zhiyong Fan & Yulong Yin

  3. UMR 914 INRA/AgroParisTech, Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, 75005, Paris, France

    Xin Wu & Francois Blachier

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  1. Xin Wu
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  2. Chunyan Xie
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  3. Yuzhe Zhang
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  4. Zhiyong Fan
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  5. Yulong Yin
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  6. Francois Blachier
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Correspondence to Xin Wu or Yulong Yin.

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Wu, X., Xie, C., Zhang, Y. et al. Glutamate–glutamine cycle and exchange in the placenta–fetus unit during late pregnancy. Amino Acids 47, 45–53 (2015). https://doi.org/10.1007/s00726-014-1861-5

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