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Transport of amino acids through the placenta and their role

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Abstract

Amino acids are transported across the human placenta mediated by transporter proteins that differ in structure, mechanism and substrate specificity. Some of them are Na+-dependent systems, whereas others are Na+-independent. Among these there are transporters composed of a heavy chain, a glycoprotein, and a light chain. Moreover, they can be differently distributed in the two membranes forming the syncytiotrophoblast. The transport mechanisms involved and their regulation are only partially known. In the placenta itself, part of the amino acids is metabolized to form other compounds important for the fetus. This occurs for instance for arginine, which gives rise to polyamines and to NO. Interconversion occurs among few other amino acids Transport is altered in pregnancy complications, such as restricted fetal growth.

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References

  • Adler V, Yin Z, Fuchs SV, Benezra M, Rosario L, Tew KD, Pincus MR, Sardana M, Henderson CJ, Wolf CR, Davis RJ, Ronai Z (1999) Regulation of JNK signaling by GSTp. EMBO J 18:1321–1334

    Article  PubMed  CAS  Google Scholar 

  • Ali M, Buhimschi I, Chwalisz K, Garfielf RE (1997) Changes in expression of the nitric oxide synthase isoforms in rat uterus and cervix during pregnancy and parturition. Mol Hum Reprod 3:995–1003

    Article  PubMed  CAS  Google Scholar 

  • Ayuk PTY, Sibley CP, Donnai P, D’Souza S, Glazier JD (2000) Development and polarization of cationic amino acid transporters and regulators in the human placenta. Am J Physiol 278:C1162–C1171

    CAS  Google Scholar 

  • Babu E, Kanai Y, Chairoungdua A, Kim DK, Iribe Y, Tangtrongsup S, Jutabha P, Li Y, Ahmrd N, Sakamoto S, Anzai N, Nagamori S, Endou H (2003) Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J Biol Chem 278:43838–43845

    Article  PubMed  CAS  Google Scholar 

  • Battaglia FC (2000) Glutamine and glutamate exchange between the fetal liver and the placenta. J Nutr 130:974S–977S

    PubMed  CAS  Google Scholar 

  • Baylis SA, Strijbos PJLM, Russell RJ, Rijhsinghani A, Charles IG, Weiner CP (1999) Temporal expression of inducible nitric oxide synthase in mouse and human placenta. Mol Hum Reprod 5:277–286

    Article  PubMed  CAS  Google Scholar 

  • Bodoy S, Martin L, Zorzano A, Palacin M, Estévez R, Bertran J (2005) Identification of LAT4, a novel amino acid transporter with system L activity. J Biol Chem 280:12002–12011

    Article  PubMed  CAS  Google Scholar 

  • Camelo JS Jr, Jorge SM, Martinez FE (2004) Amino acid composition of parturient plasma, the intervillous space of the placenta and the umbilical vein of term newborn infants. Braz J Med Biol Res 37:711–717

    Article  PubMed  CAS  Google Scholar 

  • Cariappa R, Heath-Monnig E, Smith CH (2003) Isoforms of amino acid transporters in placental syncytiotrophoblast: plasma membrane localization and potential role in maternal/fetal transport. Placenta 24:713–726

    Article  PubMed  CAS  Google Scholar 

  • Casanello P, Escudero C, Sobrevia L (2007) Equilibrative nucleoside (ENTs) and cationic amino acid (CATs) transporters: implications in foetal endotelium dysfunction in human pregnancy diseases. Curr Vasc Pharmacol 5:69–84

    Article  PubMed  CAS  Google Scholar 

  • Cesareo E, Parker LJ, Pedersen JZ, Nuccetelli M, Mazzetti AP, Pastore A, Federici G, Caccuri AM, Ricci G, Adams JJ, Parker MW, Lo Bello M (2005) Nitrosylation of human glutathione transferase P1–1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo. J Biol Chem 280:42172–42180

    Article  PubMed  CAS  Google Scholar 

  • Cetin I (2001) Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo. Ped Res 49:148–154

    Article  CAS  Google Scholar 

  • Cetin I, Ronzoni S, Marconi AM, Perugino G, Corbetta C, Battaglia F, Pardi G (1996) Maternal concentration and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancy. Am J Obstet Gynecol 174:1575–1583

    Article  PubMed  CAS  Google Scholar 

  • Christensen HN (1990) Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev 70:43–77

    PubMed  CAS  Google Scholar 

  • Closs EI, Boissel J-P, Habermeier A, Rotmann A (2006) Structure and function of cationic amino acid transporters (CATs). J Membr Biol 213:67–77

    Article  PubMed  CAS  Google Scholar 

  • Desforges M, Lacey HA, Glazier JD, Greenwood SL, Mynett KJ, Speake PF, Sibley CP (2006) SNAT4 isoform of system A amino acid transporter is expressed in human placenta. Am J Physiol Cell Physiol 290: C305–C312

    Article  PubMed  CAS  Google Scholar 

  • Diaz D, Krejsa CM, Kavanagh TJ (2002) Expression of glutamate-cysteine ligase during mouse development. Mol Reprod Dev 62:83–91

    Article  PubMed  CAS  Google Scholar 

  • Diaz D, Krejsa CM, White CC, Charleston JS, Kavanagh TJ (2004) Effect of methylmercury on glutamate-cysteine ligase expression in the placenta and yolk sac during mouse development. Reprod Toxicol 19:117–129

    Article  PubMed  CAS  Google Scholar 

  • Dicke JM, Verges D, Kelley LK, Smith CH (1993) Glycine uptake by microvillous and plasma basal membrane vesicles from term human placentae. Placenta 14:85–89

    Article  PubMed  CAS  Google Scholar 

  • Eleno N, Devés R, Boyd CA (1994) Membrane potential dependence of the kinetics of cationic amino acid transport systems in human placenta. J Physiol 479:291–300

    PubMed  CAS  Google Scholar 

  • Fontana L, Cravanzola C, Colombatto S, Grillo MA (1996) JAR human placental choriocarcinoma cells actively synthesize, take up and release polyamines. Cell Biochem Funct 14:173–180

    PubMed  CAS  Google Scholar 

  • Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB (2002) Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 196:459–468

    Article  PubMed  CAS  Google Scholar 

  • Fukasawa Y, Segawa H, Kim JY, Chairoungdua A, Kim DK, Matsuo H, Cha SH, Endou H, Kanai Y (2000) Identification and characterization of a Na+-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral d- and l-amino acids. J Biol Chem 275:9690–9698

    Article  PubMed  CAS  Google Scholar 

  • González A, López AS, Alcázar JL, López-Moratalla N (2004) Does nitric oxide play a role in maternal tolerance towards the foetus? J Physiol Biochem 60:227–238

    Article  PubMed  Google Scholar 

  • Hoeltzli SD, Kelley LK, Moe AJ, Smith CH (1990) Anionic amino acid transport systems in isolated basal plasma membrane of human placenta. Am J Physiol 259:C47–C55

    PubMed  CAS  Google Scholar 

  • Ishida M, Hiramatsu Y, Masuyama H, Mizutani Y, Kudo T (2002) Inhibition of placental ornithine decarboxylase by DL-a-difluoro-methylornithine causes fetal growth restriction in rat. Life Sci 70:1395–1405

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa T, Harada T, Koi H, Kubota T, Azuma H, Aso T (2007) Identification of arginase in human placental villi. Placenta 28:133–138

    Article  PubMed  CAS  Google Scholar 

  • Jansson T (2001) Amino acid transporters in the human placenta. Pediatr Res 49:141–147

    Article  PubMed  CAS  Google Scholar 

  • Jansson N, Petersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M, Ganapathy V, Powell TL, Jansson T (2006) Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576:935–946

    Article  PubMed  CAS  Google Scholar 

  • Józwik M,Teng C, Wilkening RB, Meschia G, Battaglia FC (2004) Reciprocal inhibition of umbilical uptake within groups of amino acids. Am J Physiol Endocrinol Metab 286:E376–E383

    Article  PubMed  Google Scholar 

  • Kalhan SC, Parimi PS (2006) Transamination of leucine and nitrogen accretion in human pregnany and the newborn infant. J Nutr 136:281S–287S

    PubMed  CAS  Google Scholar 

  • Karl PI, Tkaczevski H, Fisher SE (1990) Characteristcs of histidine uptake by human placental microvillous membrane vesicles. Pediatr Res 25:19–26

    Article  Google Scholar 

  • Kim DK, Kanai Y, Chairoungdu A, Matsuo H, Cha SH, Endou H (2001) Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem 276:17221–17228

    Article  PubMed  CAS  Google Scholar 

  • Klatt P, Lamas S (2000) Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 267:4928–4944

    Article  PubMed  CAS  Google Scholar 

  • Kudo Y, Boyd CAR (1990) Human placental l-tyrosine transport: a comparison of brush-border and basal membrane vesicles. J Physiol 426:381–395

    PubMed  CAS  Google Scholar 

  • Kudo Y, Boyd CAR (2001a) Characterisation of l-tryptophan transporters in human placenta: a comparison of brush border and basal membrane vesicle. J Physiol 531:405–416

    Article  PubMed  CAS  Google Scholar 

  • Kudo Y, Boyd CAR (2001b) The physiology of human evasion during pregnancy; the critical role of placental tryptophan metabolism and transport. Pflügers Arch/Eur J Physiol 442:639–641

    Article  CAS  Google Scholar 

  • Kulanthaivel P, Cool DR, Ramamoorthy S, Mahesh VB, Leibach FH, ganapathy V (1991) Transport of taurine and its regulation by protein kinase C in the JAR human placental choriocarcinoma cell line. Biochem J 277:53–58

    PubMed  CAS  Google Scholar 

  • Kwon H, Wu G, Bazer FW, Spencer TE (2003) Developmental changes in polyamine levels and synthesis in the ovine conceptus. Biol Reprod 69:1626–1634

    Article  PubMed  CAS  Google Scholar 

  • Lewis RM, Godfrey KM, Jackson AA, Cameron IT, Hanson MA (2005) Low serine hydroxymetyltransferase activity in the human placenta has important implications for fetal glycine supply. J Clin Endocrinol Metab 90:1594–1598

    Article  PubMed  CAS  Google Scholar 

  • Lewis RM, Glazier J, Greenwood SL, Benneu EJ, Godfrey KM, Jackson AA, Sibley CP, Cameron IT, Hanson MA (2007) l-serine uptake by human placental microvillous membrane vesicles. Placenta 28:445–452

    Article  PubMed  CAS  Google Scholar 

  • López AS, Alegre E, Diaz A, Mugueta C, González A (2006) Bimodal effect of nitric oxide in the enzymatic activity of indoleamine 2,3-dioxygenase in human monocytic cells. Immunol Lett 106:163–171

    Article  PubMed  CAS  Google Scholar 

  • Malandro MS, Beveridge MJ, Kilberg MS, Novak DA (1996) Effect of a low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am J Physiol 271:C295–C303

    PubMed  CAS  Google Scholar 

  • Marconi AM, Battaglia FC, Meschia G, Sparks JW (1989) A comparison of amino acid arteriovenous differences across the liver and placenta of the fetal lamb. Am J Physiol 257:E909–E910

    PubMed  CAS  Google Scholar 

  • Mellor AL, Munn DH (1999) Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 20:469–47

    Article  PubMed  CAS  Google Scholar 

  • Mothet JP, Parent AT, Wolosker H, Brady RO Jr, Linden DJ, Ferris CD, Rogawski MA, Snyder SH (2000) d-serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor. Proc Natl Acad Sci 97:4926–4931

    Article  PubMed  CAS  Google Scholar 

  • Myatt L (2006) Placental adaptive responses and fetal programming. J Physiol 572:25–30

    PubMed  CAS  Google Scholar 

  • Norberg S, Powell TL, Jansson T (1998) Intrauterine growth restriction is associated with a reduced activity of placental taurine transporters. Pediatr Res 44:233–238

    Article  PubMed  CAS  Google Scholar 

  • Novak DA, Beveridge MJ (1997) Glutamine transport in human and rat placenta. Placenta 18:379–386

    Article  PubMed  CAS  Google Scholar 

  • Palacin M, Nunes V, Font-Litjós M, Jiménez-Vidal M, Fort J, Gasol E, Pineda M, Feliubadaló L, Chillarón J, Zorzano A (2005) The genetics of heteromeric amino acid transporters. Physiol 20:112–124

    Article  CAS  Google Scholar 

  • Phanstiel O IV, Kaur N, Delcros J-G (2007) Structure-activity investigations of polyamine–anthracene conjugates and their uptake via the polyamine transporter. Amino Acids 33:305–313

    Article  PubMed  CAS  Google Scholar 

  • Ramadan T, Camargo SMR, Herzog B, Bordin M, Pos M (2007) Recycling of amino acids via TAT1 allows efflux of neutral amino acids via LAT2–4F2hc exchanger. Pflüger Arch - Eur J Physiol 454:507–516

    Article  CAS  Google Scholar 

  • Ramamoorthy S, Leibach FH, Mahesh V, Han H, Yang-Feng T, Blakely RD, Ganapathy V (1994) Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J 300:893–900

    PubMed  CAS  Google Scholar 

  • Roos S, Jansson NL, Palmberg I, Säljö K, Powell YL, Jansson T (2007) Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted foetal growth. J Physiol 582:449–459

    Article  PubMed  CAS  Google Scholar 

  • Rotmann A, Simon A, Martiné U, Habermeier A, Closs EI (2007) Activation of classical protein kinase C (PKC) decreases transport via systems y+ and y+L. Am J Physiol Cell Physiol 292:C2259–C2268

    Article  PubMed  CAS  Google Scholar 

  • San Martin R, Sobrevia L (2006) Gestational diabetes and the adenosine/L-arginine/nitric oxide (ALANO) pathway in human umbilical vein endothelium. Placenta 27:1–10

    Article  PubMed  CAS  Google Scholar 

  • Sato H, Tamba M, Ishii T, Bannai S (1999) Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem 274:11455–11458

    Article  PubMed  CAS  Google Scholar 

  • Sharpe JG, Seidel ER (2005) Polyamines are absorbed through a y+ amino acid carrier in rat intestinal epithelial cells. Amino Acids 29:245–253

    Article  PubMed  CAS  Google Scholar 

  • Shibata E, Powers RW, Rajakumar A, von Versen-Höynck F, Gallaher MJ, Lykins DL (2006) Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation. Am J Physiol Endocrinol Metab 291:E1009–E0016

    Article  PubMed  CAS  Google Scholar 

  • Susarla BTS, Seal RP, Zelenaia O, Watson DJ, Wolfe JH, Amara SG, Robinson MB (2004) Differential regulation of GLAST immunoreactivity and activity by protein kinase C: evidence for modification of amino and carboxyl termini. J Neurochem 91:1151–1163

    Article  PubMed  CAS  Google Scholar 

  • Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, Opelz G (2002) Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J Exp Med 196:447–457

    Article  PubMed  CAS  Google Scholar 

  • Terness P, Chuang J-J, Opelz G (2006) The immunoregulatory role of IDO-producing human dendritic cells revisited. Trends Immunol 27:68–73

    Article  PubMed  CAS  Google Scholar 

  • Van Winkle LJ, Campione AL, Farrington BH (1990) Development of system B0,+ and a broad-scope Na+-dependent transporter of zwitterionic amino acids in preimplantation mouse conceptuses. Biochim Biophys Acta 1025:225–233

    Article  PubMed  Google Scholar 

  • Van Winkle LJ, Tesch JK, Shah A, Campione AL (2006) System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood. Hum Reprod Update 12:145–157

    Article  PubMed  CAS  Google Scholar 

  • Vásquez G, Sanhueza F, Vásquez R, González M, San Martin R, Casanello P, Sobrevia L (2004) Role of adenosine transport in gestational diabetes-induced l-arginine transport and nitric oxide synthesis in human umbilical vein endothelium. J Physiol 560:111–122

    Article  PubMed  CAS  Google Scholar 

  • Verrey F, Meier C, Rossier G, Kühn L (2000) Glycoprotein-associated amino acid exchangers: broadening the range of transport specificity. Pflügers Arch/Eur J Physiol 440:503–512

    CAS  Google Scholar 

  • Wagner CA, Lang F, Bröer S (2001) Function and structure of heterodimeric amino acid transporters. Am J Physiol Cell Physiol 281:C1077–C1093

    PubMed  CAS  Google Scholar 

  • Wang T, Arifoglu P, Ronai Z, Tew KD (2001) Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C-terminus. J Biol Chem 276:20999–21003

    Article  PubMed  CAS  Google Scholar 

  • Wellner VP, Sekura R, Meister A., Larsson A (1974) Glutathione synthetase deficiency, an inborn error of metabolism involving the γ-glutamyl cycle in patients with oxoprolinuria (pyroglutamic aciduria). Proc Natl Acad Sci 71:2505–2509

    Article  PubMed  CAS  Google Scholar 

  • White MF (1985) The transport of cationic amino acids across the plasma membrane of mammalian cells. Biochem Biophys Acta 822:355–374

    PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Hu J, Johnson GA, Spencer TE (2005) Polyamine synthesis from proline in the developing porcine placenta. Biol Reprod 72:842–850

    Article  PubMed  CAS  Google Scholar 

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  1. Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Biochimica, Università di Torino, Via Michelangelo 27, 10126, Torino, Italy

    M. A. Grillo, A. Lanza & S. Colombatto

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  1. M. A. Grillo
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  2. A. Lanza
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  3. S. Colombatto
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Correspondence to M. A. Grillo.

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Grillo, M.A., Lanza, A. & Colombatto, S. Transport of amino acids through the placenta and their role. Amino Acids 34, 517–523 (2008). https://doi.org/10.1007/s00726-007-0006-5

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