title: Mechanism of clearance and transfer of dipeptides by perfused human placenta.
abstract: Glycylglutamine (Gly-Gln) is stable source of glutamine for parenteral nutrition. In the present study we have investigated whether this dipeptide is transferred intact across the human placenta. Although after 90 min of placental perfusion there was almost complete disappearance of Gly-Gln (100 microM) from the maternal compartment, only a small concentration of this dipeptide (< 6 microM) appeared in the fetal compartment. To investigate whether this transfer was due to transcellular transport, brush-border membrane vesicles of the human placenta were probed with [3H]Gly-Gln, which showed no uptake. To investigate whether hydrolysis was the mechanism of disappearance of Gly-Gln, the perfusion study was repeated with glycylsarcosine (Gly-Sar), which is resistant to hydrolysis. In sharp contrast to Gly-Gln, after 90 min of perfusion nearly 80% of Gly-Sar remained in the perfusate (half-life of 24 vs. 235 min). The rest of the Gly-Sar was recovered intact in the fetal compartment. The addition of Gly-Gln to the maternal compartment increased the accumulation of glycine, but not glutamine, in both the maternal and fetal compartments. In conclusion, our data suggest that 1) the mechanism of clearance of Gly-Gln by perfused human placenta is largely hydrolysis, whereas that of Gly-Sar is largely passive diffusion, and 2) the placenta has a greater preference for glutamine than for glycine.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Adibi
authors.forename: S
authors.initials: S
authors.lastname: Schenker
authors.forename: E
authors.initials: E
authors.lastname: Morse
mesh_terms: D004151:Dipeptides / Q000378:metabolism*; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D004151:Dipeptides; C039788:glycylglutamine