MECHANISM OF CLEARANCE AND TRANSFER OF DIPEPTIDES BY PERFUSED HUMAN PLACENTA

Glycylglutamine (Gly-Gln) is a stable source of glutamine for parenter al nutrition. In the present study we have investigated whether this d ipeptide is transferred intact across the human placenta. Although aft er 90 min of placental perfusion there was almost complete disappearan ce of Gly-Gln (100 mu M) from the maternal compartment, only a small c oncentration of this dipeptide (<6 mu M) appeared in the fetal compart ment. To investigate whether this transfer was due to transcellular tr ansport, brush-border membrane vesicles of the human placenta were pro bed with [H-3]Gly-Gln, which showed no uptake. To investigate whether hydrolysis was the mechanism of disappearance of Gly-Gln, the perfusio n study was repeated with glycylsarcosine (Gly-Sar), which is resistan t to hydrolysis. In sharp contrast to Gly-Gln, after 90 min of perfusi on 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 incre ased the accumulation of glycine, but not glutamine, in both the mater nal and fetal compartments. In conclusion, our data suggest that I) th e mechanism of clearance of Gly-Gln by perfused human placenta is larg ely hydrolysis, whereas that of Gly-Sar is largely passive diffusion, and 2) the placenta has a greater preference for glutamine than for gl ycine.