Folate-binding proteins

J. Holm, S. I. Hansen, K. Sondergaard, and M. Hoier-Madsen. The high-affinity folate binding protein in normal and malignant mammary gland tissue. Adv. Exp. Med. Biol. 338 757-760 (1993). 

A. Tomassetti, L. R. Coney, S. Canevari, S. Miotti, P. Facheris, V. R. J. Zurawski, and M. I. Colnaghi. Isolation and biochemical characterization of the soluble and membrane forms of folate binding protein expressed in the ovarian carcinoma cell line IGROV1. FEBS Lett. 317 143-146 (1993). 

Bekaert et al., 2007 Rebeille et al., 2006) and include increasing the proportion of 5-formyl-THF, the most stable natural folate, sequestering folates into vacuoles, increasing folate salvage capacity or over-expressing folate-binding protein of plant (yet to be identified) or mammalian (Jones and Nixon, 2002) origin in plant cells. 

Jones, M. L, Nixon, P. F. (2002). Tetrahydrofolates are greatly stabilized by binding to bovine milk folate-binding protein. J. Nutr., 132,2690-2694. 

Yeo E, Wagner C (1994) Tissue binding of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A 91 210-214... 

A folate-binding protein (FBP) has been isolated from cow s milk by affinity chromatography on sepharose to which folate has been attached (Salter et al. 1972). Cow s milk contains -8 mg FBP per liter. The protein has a molecular weight of 35,000. Cow s milk has also been shown to bind vitamin Bi2, but the protein responsible has not been isolated from this source, although it has been obtained from the milks of other species (Burger and Allen 1974). 

Folic acid, shown in Fig. 12.3, is a common component of food and vitamins.36 The receptor for the vitamin folic acid is known as the folate receptor or the high-affinity membrane folate-binding protein.37 These folate receptors typically are not present in normal cells, but in a variety of human tumors they are greatly overexpressed.36-38 In addition, folate receptors mediate internalization by endocytosis. For these reasons, folic acid has been examined as a homing device. In general, studies have shown that by simple conjugation of folic acid to macromolecules, internalization into cells can occur similarly to that of free folic acid.39... 

Flansen, D. K., Streck, R. D., and Antony, A. C. (2003). Antisense modulation of the coding or regulatory sequence of the folate receptor (folate binding protein-1) in mouse embryos leads to neural tube defects. Birth Defects Res. Part A Clin. Mol. Teratol. 67(7), 475 487. 

Saitsu, H., Ishibashi, M., Nakano, H., and Shiota, K. (2003). Spatial and temporal expression of folate-binding protein 1 (Folbpl) is closely associated with anterior neural tube closure in mice. Dev. Dyn. 226(1), 112-117. 

Spiegelstein, O., Mitchell, L. E., Merriweather, M. Y., Wicker, N. J., Zhang, Q., Lammer, E. J., and Finnell, R. H. (2004). Embryonic development of folate binding protein-1 (Folbpl) knockout mice Effects of the chemical form, dose, and timing of maternal folate supplementation. Dev. Dyn. 231(1), 221-231. 

Bovine milk also contains binding proteins for vitamins B12, folic acid and riboflavin. It has been suggested that the folate-binding protein contributes to the absorption of folate in the intestines (Parodi, 1998). 

Demethylated tetrahydrofolate monoglutamate is released hy extrahepatic tissues and is transported hound to a plasma folate binding protein similar to that in milk. It has a very low affinity for methyl-tetrahydrofolate and other one-carbon substituted derivatives. It functions mainly to return folate to the liver, where it is either conjugated for storage or methylated to 5-methyl-tetrahydrofolate that is secreted in the bile. 

There is very little urinary loss of folate, some 5 to 10 nmol of microbiologically active material per day. Not only is most folate in plasma bound to proteins (either folate binding protein for unsubstituted folate or albumin for methyl-tetrahydrofolate), and thus protected from glomerular filtration, but also the renal brush border has a high concentration of folate binding protein that acts to reabsorb any that is filtered. 

Weitman S, Anderson RGW, and Kamen BA (1994) Folate binding proteins. In Vitamin Receptors Vitamins as Ligands in Cell Communication, K Dakshinamurti (ed.), pp. 106-36. Cambridge, UK Cambridge University Press. 

Min H, Shane B, and Stokstad EL (1988) Identification of 10-formyltetrahydrofolate dehydrogenase-hydrolase as a major folate binding protein in liver cytosol. Bio-... 

Folate binding protein has been prepared from goat s milk by adsorption to a methotrexate-Sepharose column [94]. The folate binding protein was then coupled to cyanogen bromide activated Sepharose and used in the purification of folates and for the removal of endogenous folates from reaction mixtures. Cortisol hemisuccinate coupled to an amino Sepharose has been used to purify glucocorticoid binding protein(s) from rat liver... 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

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