The placenta is vital to the survival of the fetus because it provides the growing fetus with nutrition and oxygen and it excretes the fetal metabolic waste products. Several classes of nutrients are transferred from the mother to the fetus across the placenta. Interference with this function of the placenta invariably results in growth retardation of the fetus and reduces its chances of survival. Therefore, there is a profound need for information relating to the role of the placenta as a nutritional organ. Amino acids represent an important class of nutrients because they are obligatory as the building blocks for protein synthesis and as precursors for many biologically active compounds which are vital to the well-being of the fetus. Most amino acids are transported across the placenta by energy-dependent processes. The energy-requiring step is primarily located at the brush border membrane of the placenta. The proposed studies will therefore be conducted by using brush border membrane vesicles isolated from human term placentas. Human placenta is a disposable tissue and use of this tissue as the experimental tool offers a unique opportunity to investigate placental function without safety and ethical concerns. Moreover, direct use of the human placentas rather than the placentas from laboratory animals removes the need for unnecessary, and sometimes even incorrect and misleading, extrapolation of the results from non-human species to humans. Virtually nothing is known at present about the molecular mechanisms of amino acid transfer across the placenta. This project proposes a series of investigations designed to look into this aspect.
The specific aims of the project include delineation of the role of ion gradients other than a sodium gradient as the energy source for placental amino acid transport, determination of the chemical nature of the active site of amino acid transport systems, and purification and characterization of the proteins which make up these transport systems. Substances such as ethanol, cannabinoids and various drugs interfere with placental amino acid transport and consequently have toxic effects on fetal growth and development. A detailed knowledge of the chemical nature of the placental amino acid transport systems is not only important to understand the placenta amino acid transfer under physiological conditions, but also to understand the mechanisms by which the above- mentioned feto-toxic agents affect the function of these transport systems.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical College of Georgia (MCG)
Schools of Medicine
United States
Zip Code
Torres-Zamorano, V; Leibach, F H; Ganapathy, V (1998) Sodium-dependent homo- and hetero-exchange of neutral amino acids mediated by the amino acid transporter ATB degree. Biochem Biophys Res Commun 245:824-9
Wu, X; Prasad, P D; Leibach, F H et al. (1998) cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun 246:589-95
Prasad, P D; Wang, H; Kekuda, R et al. (1998) Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate. J Biol Chem 273:7501-6
Kekuda, R; Torres-Zamorano, V; Fei, Y J et al. (1997) Molecular and functional characterization of intestinal Na(+)-dependent neutral amino acid transporter B0. Am J Physiol 272:G1463-72
Prasad, P D; Ramamoorthy, S; Leibach, F H et al. (1997) Characterization of a sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin and lipoate in human placental choriocarcinoma cells. Placenta 18:527-33
Roque, A S; Prasad, P D; Bhatia, J S et al. (1996) Sodium-dependent high-affinity binding of carnitine to human placental brush border membranes. Biochim Biophys Acta 1282:274-82
Prasad, P D; Huang, W; Ramamoorthy, S et al. (1996) Sodium-dependent carnitine transport in human placental choriocarcinoma cells. Biochim Biophys Acta 1284:109-17
Kekuda, R; Prasad, P D; Fei, Y J et al. (1996) Cloning of the sodium-dependent, broad-scope, neutral amino acid transporter Bo from a human placental choriocarcinoma cell line. J Biol Chem 271:18657-61
Jayanthi, L D; Ramamoorthy, S; Mahesh, V B et al. (1995) Substrate-specific regulation of the taurine transporter in human placental choriocarcinoma cells (JAR). Biochim Biophys Acta 1235:351-60
Yang-Feng, T L; Ma, Y Y; Liang, R et al. (1995) Assignment of the human folate transporter gene to chromosome 21q22.3 by somatic cell hybrid analysis and in situ hybridization. Biochem Biophys Res Commun 210:874-9

Showing the most recent 10 out of 37 publications