Effect of a Folate–Binding Protein on the Plasma Transport and Tissue Distribution of Folic Acid

Rubinoff, Mitchell; Abramson, Ruth G.; Schreiber, Carol; Waxman, Samuel

doi:10.1159/000207170

Cited by 13 publications

(4 citation statements)

References 18 publications

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“…In other words, such a process could serve as a means for better salvaging folates under more limiting conditions. Certainly, it is known that liver uptake of FA is dramatically increased when injected into circulation as a precomplex with the soluble form of the FR (Fernandes-Costa and Metz, 1979;Rubinoff et al, 1981). Plus, we have observed a near 500% increase of 99m Tc-EC20 uptake in liver, also when injected into circulation as a FR precomplex (Endocyte, Inc., unpublished data).…”

mentioning

confidence: 53%

Impact of High and Low Folate Diets on Tissue Folate Receptor Levels and Antitumor Responses Toward Folate-Drug Conjugates

Leamon

Reddy²,

Dorton³

et al. 2008

J Pharmacol Exp Ther

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Herein, we present a detailed analysis on the effects of feeding laboratory mice both high and low folic acid (folate)-containing diets as related to associated changes in serum and red blood cell (RBC) folate levels, tissue-derived folate receptor levels, and the ability of folate-drug conjugates to bind and effectuate activity against folate receptor (FR)-positive tumor xenografts. Our data show that serum and RBC folate concentrations sharply drop immediately after mice are switched to low folate diets; however, both parameters reach steady-state, "humanlike" levels after 6 weeks. Interestingly, tissue-related folate binding capacities were also lowered during the dietary modulation period, whereas the net uptake of a radiolabeled folate conjugate was simultaneously increased 2.6-and 5-fold in FR-positive kidney and tumor tissue, respectively. Finally, the performances of several clinically and preclinically relevant folate-drug conjugates were evaluated against tumors in mice that were fed high or low folate diets. Except when administered at a dose level 6-fold less than that required to saturate endogenous FRs, no significant loss of antitumor activity was observed. From these findings, we conclude that lowering the dietary intake of folates in mice has little impact on the biological activity of repetitively dosed folate-targeted agents but that low folate diet regimens will reduce serum and RBC folate levels down to levels that more closely approximate the normal human ranges.

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mentioning

confidence: 53%

Impact of High and Low Folate Diets on Tissue Folate Receptor Levels and Antitumor Responses Toward Folate-Drug Conjugates

Leamon

Reddy²,

Dorton³

et al. 2008

J Pharmacol Exp Ther

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“…Since the so-called specific folate-binding proteins are believed to have the function of binding folates for storage [11], their presence in the placenta may account for the folate concentrations observed in this organ. It has long been believed that the fetus removes folates from a compartment having lower concentrations of this vitamin that the fetus's own levels.…”

Section: Discussionmentioning

confidence: 99%

Serum and red blood cell folate levels in parturients, in the intervillous space of the placenta and in full-term newborns

Giugliani¹,

Jorge²,

Gonçalves³

1985

Journal of Perinatal Medicine

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“…It is possible that the serum folate binder has no significant physiological function and arises only by random or accidental cleavage from the surface of cells (92). Alternatively, serum sFBP could act as a minor storage protein to conserve folates (20, 93), or it could serve as a means for selectively clearing the serum of folic acid or other oxidized folate compounds (65).…”

Section: Serum Folate-binding Proteinsmentioning

confidence: 99%

Folate-Binding Proteins

1990

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Folate-binding proteins of three major classes have been observed in various bodily fluids and in the plasma membrane and cytoplasm of normal and neoplastic cells. A major class, the high-affinity folate-binding proteins, show a preferential and tight binding of folic acid relative to reduced folates and methotrexate and consist of water-soluble and membrane-associated forms. Soluble forms of the high-affinity binders are present in serum and milk and in the growth medium of certain cultured cell lines, whereas membrane-associated forms are observed on the surface of various cells and tissues. The binders in serum have no clearly defined function, whereas the milk binders serve to accumulate and stabilize reduced-folate compounds in milk and they may also facilitate the absorption of folates by the intestinal mucosa of neonates. Membrane-bound forms of high-affinity folate-binding proteins mediate the transport of folate compounds across plasma membranes and appear to utilize endocytosis as the transport mechanism. Membrane-associated high-affinity binding proteins contain covalently bound phospholipids and hydrophobic C-terminal amino acid sequences that are absent in the soluble forms. The remaining protein portions of these binders show considerable sequence homology. The second class is composed of folate-binding proteins that reside solely in the plasma membrane and are structurally and mechanistically distinct from the high-affinity binders. These proteins function in transport, exhibit varied substrate specificities that accommodate reduced-folate compounds with equal or higher affinity than folate, and do not utilize endocytosis as the mechanism for substrate internalization. The third class of folate-binding proteins consists of enzymes that reside in the cytoplasm of cells.

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Effect of a Folate–Binding Protein on the Plasma Transport and Tissue Distribution of Folic Acid

Cited by 13 publications

References 18 publications

Impact of High and Low Folate Diets on Tissue Folate Receptor Levels and Antitumor Responses Toward Folate-Drug Conjugates

Impact of High and Low Folate Diets on Tissue Folate Receptor Levels and Antitumor Responses Toward Folate-Drug Conjugates

Serum and red blood cell folate levels in parturients, in the intervillous space of the placenta and in full-term newborns

Folate-Binding Proteins

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