Serine racemase and D-serine transport in human placenta and evidence for a transplacental gradient for D-serine in humans

Zhong Chen, Wei Huang, Sonne R. Srinivas, Chandra R. Jones, Vadivel Ganapathy, Puttur D Prasad

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective To investigate the possible role of human placenta in providing D-serine to the developing fetus. Methods Expression of serine racemase in placenta was determined by reverse transcriptase polymerase chain reaction and northern analysis and confirmed by subsequent cloning. The transport of D-serine by human ATB0 was characterized by expressing the cloned cDNA transiently in mammalian cells using the vaccinia virus expression system. D-serine levels in maternal and fetal blood were measured by fluorescence high-performance liquid chromatography (HPLC) after derivatization of the amino acids with o-phthaldialdehyde and N-tertiary-butyloxycarbonyl-L-cysteine. Results mRNA for serine racemase was detected in placenta. ATB0 was capable of D-serine transport, and the transport process is obligatorily dependent on sodium (Na+) with a Na+:substrate stoichiometry of 1:1 and saturable with a Michaelis-Menten constant of 310 ± 30 μM. Furthermore, studies have shown that ATB0 is not expressed in the maternal-facing brush border membrane of human placental syncytiotrophoblast. The circulating concentration of D-serine in maternal serum is 5.8 ± 0.5 μM, and the corresponding value in the fetal serum is 14.6 ± 1.2 μM, indicating a two- to three-fold higher concentration of D-serine in the fetus than in the mother. Conclusion We speculate that D-serine is synthesized in human placenta by the racemization of L-serine and that ATB0, expressed on the basal membrane of the syncytiotrophoblast, mediates the efflux of D-serine into the fetal circulation in exchange for other amino acids in fetal blood.

Original languageEnglish (US)
Pages (from-to)294-303
Number of pages10
JournalJournal of the Society for Gynecologic Investigation
Volume11
Issue number5
DOIs
StatePublished - Jul 1 2004

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Serine
Placenta
Mothers
Trophoblasts
Fetal Blood
Fetus
o-Phthalaldehyde
serine racemase
Amino Acids
Membranes
Vaccinia virus
Microvilli
Reverse Transcriptase Polymerase Chain Reaction
Serum
Cysteine
Organism Cloning
Complementary DNA
Fluorescence
Sodium
High Pressure Liquid Chromatography

Keywords

  • Trophoblast
  • amino acid
  • development
  • transplacental
  • transport

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Serine racemase and D-serine transport in human placenta and evidence for a transplacental gradient for D-serine in humans. / Chen, Zhong; Huang, Wei; Srinivas, Sonne R.; Jones, Chandra R.; Ganapathy, Vadivel; Prasad, Puttur D.

In: Journal of the Society for Gynecologic Investigation, Vol. 11, No. 5, 01.07.2004, p. 294-303.

Research output: Contribution to journalArticle

Chen, Zhong ; Huang, Wei ; Srinivas, Sonne R. ; Jones, Chandra R. ; Ganapathy, Vadivel ; Prasad, Puttur D. / Serine racemase and D-serine transport in human placenta and evidence for a transplacental gradient for D-serine in humans. In: Journal of the Society for Gynecologic Investigation. 2004 ; Vol. 11, No. 5. pp. 294-303.
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abstract = "Objective To investigate the possible role of human placenta in providing D-serine to the developing fetus. Methods Expression of serine racemase in placenta was determined by reverse transcriptase polymerase chain reaction and northern analysis and confirmed by subsequent cloning. The transport of D-serine by human ATB0 was characterized by expressing the cloned cDNA transiently in mammalian cells using the vaccinia virus expression system. D-serine levels in maternal and fetal blood were measured by fluorescence high-performance liquid chromatography (HPLC) after derivatization of the amino acids with o-phthaldialdehyde and N-tertiary-butyloxycarbonyl-L-cysteine. Results mRNA for serine racemase was detected in placenta. ATB0 was capable of D-serine transport, and the transport process is obligatorily dependent on sodium (Na+) with a Na+:substrate stoichiometry of 1:1 and saturable with a Michaelis-Menten constant of 310 ± 30 μM. Furthermore, studies have shown that ATB0 is not expressed in the maternal-facing brush border membrane of human placental syncytiotrophoblast. The circulating concentration of D-serine in maternal serum is 5.8 ± 0.5 μM, and the corresponding value in the fetal serum is 14.6 ± 1.2 μM, indicating a two- to three-fold higher concentration of D-serine in the fetus than in the mother. Conclusion We speculate that D-serine is synthesized in human placenta by the racemization of L-serine and that ATB0, expressed on the basal membrane of the syncytiotrophoblast, mediates the efflux of D-serine into the fetal circulation in exchange for other amino acids in fetal blood.",
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AU - Jones, Chandra R.

AU - Ganapathy, Vadivel

AU - Prasad, Puttur D

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N2 - Objective To investigate the possible role of human placenta in providing D-serine to the developing fetus. Methods Expression of serine racemase in placenta was determined by reverse transcriptase polymerase chain reaction and northern analysis and confirmed by subsequent cloning. The transport of D-serine by human ATB0 was characterized by expressing the cloned cDNA transiently in mammalian cells using the vaccinia virus expression system. D-serine levels in maternal and fetal blood were measured by fluorescence high-performance liquid chromatography (HPLC) after derivatization of the amino acids with o-phthaldialdehyde and N-tertiary-butyloxycarbonyl-L-cysteine. Results mRNA for serine racemase was detected in placenta. ATB0 was capable of D-serine transport, and the transport process is obligatorily dependent on sodium (Na+) with a Na+:substrate stoichiometry of 1:1 and saturable with a Michaelis-Menten constant of 310 ± 30 μM. Furthermore, studies have shown that ATB0 is not expressed in the maternal-facing brush border membrane of human placental syncytiotrophoblast. The circulating concentration of D-serine in maternal serum is 5.8 ± 0.5 μM, and the corresponding value in the fetal serum is 14.6 ± 1.2 μM, indicating a two- to three-fold higher concentration of D-serine in the fetus than in the mother. Conclusion We speculate that D-serine is synthesized in human placenta by the racemization of L-serine and that ATB0, expressed on the basal membrane of the syncytiotrophoblast, mediates the efflux of D-serine into the fetal circulation in exchange for other amino acids in fetal blood.

AB - Objective To investigate the possible role of human placenta in providing D-serine to the developing fetus. Methods Expression of serine racemase in placenta was determined by reverse transcriptase polymerase chain reaction and northern analysis and confirmed by subsequent cloning. The transport of D-serine by human ATB0 was characterized by expressing the cloned cDNA transiently in mammalian cells using the vaccinia virus expression system. D-serine levels in maternal and fetal blood were measured by fluorescence high-performance liquid chromatography (HPLC) after derivatization of the amino acids with o-phthaldialdehyde and N-tertiary-butyloxycarbonyl-L-cysteine. Results mRNA for serine racemase was detected in placenta. ATB0 was capable of D-serine transport, and the transport process is obligatorily dependent on sodium (Na+) with a Na+:substrate stoichiometry of 1:1 and saturable with a Michaelis-Menten constant of 310 ± 30 μM. Furthermore, studies have shown that ATB0 is not expressed in the maternal-facing brush border membrane of human placental syncytiotrophoblast. The circulating concentration of D-serine in maternal serum is 5.8 ± 0.5 μM, and the corresponding value in the fetal serum is 14.6 ± 1.2 μM, indicating a two- to three-fold higher concentration of D-serine in the fetus than in the mother. Conclusion We speculate that D-serine is synthesized in human placenta by the racemization of L-serine and that ATB0, expressed on the basal membrane of the syncytiotrophoblast, mediates the efflux of D-serine into the fetal circulation in exchange for other amino acids in fetal blood.

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