Neonatal role of milk folate-binding protein: studies on the course of digestion of goat's milk folate binder in the 6-d-old kid

Salter, D. N.; Mowlem, Alan

doi:10.1079/bjn19830130

Cited by 25 publications

(6 citation statements)

References 24 publications

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“…FBP is present in different biological, secretory fluids, including saliva and semen, and in particular milk [4][5][6][7][8][9]. The significance of these folate binders is largely unknown, but it has been suggested that milk FBP, shown to be resistant to gastric digestion [27], may play a role in folate uptake in the neonate intestine [10][11][12]. The present study shows that megalin, a large, multiligand, endocytic receptor expressed in the intestine and other absorptive epithelia binds and mediates the internalization of FBP.…”

Section: Discussionmentioning

confidence: 99%

Megalin binds and mediates cellular internalization of folate binding protein

Birn

Zhai

Holm³

et al. 2005

The FEBS Journal

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Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol‐linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva and semen. The function and significance of FBPs are unresolved, however, it has been suggested that they may facilitate folate uptake, e.g. during suckling. The present study shows that megalin, a large, multiligand endocytic receptor and member of the low‐density lipoprotein‐receptor family, is able to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of 125I‐labeled folate binding protein (FBP) to sections of kidney proximal tubule, known to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin‐mediated uptake, reveal 125I‐labeled FBP uptake which is inhibited by receptor associated protein and by antimegalin antibodies. Microinjection of 125I‐labeled FBP into renal tubules in vivo shows proximal tubular uptake by endocytosis. Megalin is expressed in several absorptive epithelia, including intestine and kidney proximal tubule, and thus the present findings provide a mechanism for intestinal and renal endocytic uptake of soluble FBP.

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Section: Discussionmentioning

confidence: 99%

Megalin binds and mediates cellular internalization of folate binding protein

Birn

Zhai

Holm³

et al. 2005

The FEBS Journal

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“…mFBPs have been found in tissues from placenta (4, 6, 17, 25, 60,89,90), proximal kidney tubules (13, [77][78][79][80][81], choroid plexus (86), small intestine (79), and liver (14). sFBPs are present in human (3,7,58,76,87,94), bovine (7,26,87,88), and goat (66,72) milk, in the growth medium from human KB cells (18,45) and cultured human lympho cytes (15), in normal human serum (57,93), and in umbilical cord serum (43). Milk and umbilical cord serum are relatively abundant sources of sFBP, whereas relatively low levels of sFBP occur in normal serum (43,92).…”

Section: Distributionmentioning

confidence: 98%

“…The mechanism of sequestering folate in human milk is very efficient, since lactation alone causes a decrease in maternal folate status (58,84) and can cause maternal folate deficiency (56). Studies in 6-day-old goat kids (72) showed that the FBP of goat milk is resistant to proteolysis by pancreatic enzymes and can survive along the length of the small intestine. Protease inhibitors inherent to milk may also assist the passage of intact binders into the small intestine (51).…”

Section: Milk 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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“…This situation was demonstrated by Salter & Mowlem (1983) who showed that a proportion of goat's milk FBP administered orally to neonatal goats survived along the length of the small intestine. In neonates, the uptake of folate bound to milk FBP occurs preferentially in the ileum as opposed to the jejunum.…”

Section: Absorption Of Milk Folate By the Suckling Infantmentioning

confidence: 95%

Folate

Ball¹

2004

Vitamins

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Neonatal role of milk folate-binding protein: studies on the course of digestion of goat's milk folate binder in the 6-d-old kid

Cited by 25 publications

References 24 publications

Megalin binds and mediates cellular internalization of folate binding protein

Megalin binds and mediates cellular internalization of folate binding protein

Folate-Binding Proteins

Folate

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