Serine racemase and D-serine transport in human placenta and evidence for a transplacental gradient for D-serine in humans.
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 ATB(0) 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. ATB(0) 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 microM. Furthermore, studies have shown that ATB(0) 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 microM, and the corresponding value in the fetal serum is 14.6 +/- 1.2 microM, indicating a two- to three-fold higher concentration of D-serine in the fetus than in the mother.


CONCLUSIONS
We speculate that D-serine is synthesized in human placenta by the racemization of L-serine and that ATB(0), 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.
Chen
Zhong
Z
Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 Laney Walker Boulevard, Augusta, GA 30912-2100, USA.
Huang
Wei
W
Srinivas
Sonne R
SR
Jones
Chandra R
CR
Ganapathy
Vadivel
V
Prasad
Puttur D
PD
D001692:Biological Transport; D003470:Culture Media; D005260:Female; D006801:Humans; D007700:Kinetics; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D019998:Racemases and Epimerases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013237:Stereoisomerism; D000099300:Serine Racemase
D003470:Culture Media; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase