This proposal will focus on two major aspects of the particulate and soluble folate binding proteins of human milk to identify (1) the factors involved in determining their quantitative and qualitative content in milk, and (2) the functional role of these folate binding proteins in the uptake of folates in the intestine. Studies on the biosynthesis of particulate folate binding proteins with respect to processing of the polypeptide backbone, glycosylation and acylation that may have a direct bearing on the membrane insertion, folate binding capacity and possible conversion to the soluble folate binding protein will be investigated in cultured mammary cells. The effect of folate deficiency on the secretion of these folate binding proteins will be investigated in lactating rats. The influence of various components of human milk, saliva, gastric, pancreatic and intestinal secretions on the structural integrity and ligand binding capacity of these proteins and their role in the uptake of folates will be identified in rat intestinal cells and brush border vesicles. In addition, the possibility of spontaneous incorporation, lipid interaction, and binding to membrane components by these human milk folate binding proteins will be studied in vitro. Finally, the role of these proteins in absorption of folates in vivo will be tested in a rat model which will closely simulates food folate absorption. These studies may allow for a comprehensive understanding of the significance of folate binding proteins of human milk and their role in the absorption of folates.

Project Start
1986-02-01
Project End
1991-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Verma, R S; Gullapalli, S; Antony, A C (1992) Evidence that the hydrophobicity of isolated, in situ, and de novo-synthesized native human placental folate receptors is a function of glycosyl-phosphatidylinositol anchoring to membranes. J Biol Chem 267:4119-27
Antony, A C (1992) The biological chemistry of folate receptors. Blood 79:2807-20
Verma, R S; Antony, A C (1992) Immunoreactive folate-binding proteins from human saliva. Isolation and comparison of two distinct species. Biochem J 286 ( Pt 3):707-15
Antony, A C; Briddell, R A; Brandt, J E et al. (1991) Megaloblastic hematopoiesis in vitro. Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes. J Clin Invest 87:313-25
Verma, R S; Antony, A C (1991) Kinetic analysis, isolation, and characterization of hydrophilic folate-binding proteins released from chorionic villi cultured under serum-free conditions. J Biol Chem 266:12522-35
Antony, A C; Verma, R S; Unune, A R et al. (1989) Identification of a Mg2+-dependent protease in human placenta which cleaves hydrophobic folate-binding proteins to hydrophilic forms. J Biol Chem 264:1911-4
Antony, A C; Kane, M A; Krishnan, S R et al. (1989) Folate (pteroylglutamate) uptake in human red blood cells, erythroid precursors and KB cells at high extracellular folate concentrations. Evidence against a role for specific folate-binding and transport proteins. Biochem J 260:401-11
Antony, A C; Verma, R S (1989) Hydrophobic erythrocyte folate binding proteins are converted to hydrophilic forms by trypsin in vitro. Biochim Biophys Acta 979:62-8
Srivastava, A; Boswell, H S; Heerema, N A et al. (1988) KRAS2 oncogene overexpression in myelodysplastic syndrome with translocation 5;12. Cancer Genet Cytogenet 35:61-71
Kane, M A; Elwood, P C; Portillo, R M et al. (1988) Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells. J Clin Invest 81:1398-406

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