B12 intrinsic factor
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Understanding the Role of Intrinsic Factor in Vitamin B12 Absorption
Introduction to Intrinsic Factor and Vitamin B12
Intrinsic factor is a glycoprotein essential for the absorption of vitamin B12 (cobalamin) in the small intestine. Vitamin B12 is crucial for red blood cell formation, neurological function, and DNA synthesis. The intrinsic factor binds to vitamin B12, forming a complex that is recognized and absorbed by specific receptors in the ileum.
Physicochemical Properties of Intrinsic Factor
Intrinsic factor and other vitamin B12-binding proteins have been isolated and studied for their physicochemical properties. These proteins, particularly from hog pyloric mucosa, show significant differences in intrinsic factor activity despite similar chemical and physical properties. Intrinsic factor contains more galactose and less galactosamine and glucosamine compared to its inactive counterparts. The molecular weight of intrinsic factor varies depending on its complexation with vitamin B12, indicating a reversible dimerization process upon binding1 4.
Measurement and Assay Techniques
Several methods have been developed to measure the intrinsic factor-vitamin B12 complex. A radioisotope dilution assay using binding intrinsic factor antibodies has been shown to be effective in measuring both labelled and unlabelled vitamin B12-intrinsic factor complexes. This method is valuable for studying physiological events in the gastrointestinal tract2. Additionally, solid-phase assays using polyacrylamide-bound intrinsic factor have been developed to measure microbiologically-available B12, providing a simple and effective diagnostic tool8.
Receptor-Mediated Endocytosis
The intrinsic factor-vitamin B12 complex is absorbed in the ileum through receptor-mediated endocytosis. Cubilin, a high-affinity receptor, facilitates this process. Cubilin also binds to apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL), indicating its role in epithelial apoA-I/HDL metabolism. This receptor is crucial for the endocytosis of the intrinsic factor-vitamin B12 complex and is involved in various physiological processes beyond vitamin B12 absorption3 5 6.
Molecular Characterization of Cubilin
Cubilin is a large glycoprotein with a unique structure comprising 27 CUB domains and 8 epidermal growth factor repeats. It binds to the intrinsic factor-vitamin B12 complex and other ligands, such as receptor-associated protein. The N-terminal region of cubilin is essential for membrane association, while specific CUB domains are responsible for ligand binding. This structural complexity allows cubilin to perform multiple functions in different tissues5 6.
Human Intrinsic Factor and Its Clinical Relevance
Human intrinsic factor has been isolated and characterized, showing high specificity and affinity for vitamin B12. It corrects vitamin B12 malabsorption in patients with pernicious anemia, demonstrating its clinical importance. The binding of vitamin B12 to intrinsic factor induces conformational changes that facilitate its recognition and absorption by receptors in the ileum9.
Conclusion
Intrinsic factor plays a critical role in the absorption of vitamin B12, a vital nutrient for various bodily functions. Understanding the physicochemical properties, measurement techniques, and receptor interactions of intrinsic factor enhances our knowledge of vitamin B12 metabolism and its clinical implications. Advances in assay methods and molecular characterization of receptors like cubilin provide valuable insights into the complex mechanisms underlying vitamin B12 absorption and its broader physiological roles.
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Most relevant research papers on this topic
Hog intrinsic factor. II. Some physicochemical properties of vitamin B12-binding fractions from hog pylorus.
Intrinsic factor from hog pylorus undergoes slow dimerization after vitamin B12 binding, with a model suggesting that the dimer may contain either 1 or 2 molecules of vitamin B12.
In Vitro StudyA radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody.
The new radioisotope dilution assay for vitamin B12-intrinsic factor complex provides a comparable measure of intrinsic factor with other assays, but can measure unlabelled complexes, potentially revealing two types of binding intrinsic factor antibodies.
In Vitro StudyThe intrinsic factor–vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein
Cubilin is a receptor in epithelial apolipoprotein A-I/HDL metabolism, facilitating endocytosis of high-density lipoprotein and playing a role in intestinal apoA-I metabolism.
In Vitro Study
Highly CitedHog intrinsic factor. I. Isolation of vitamin B12-binding fractions from hog pylorus.
Intrinsic factor and another high capacity vitamin B12-binding protein were isolated from hog pyloric mucosa, facilitating vitamin B12 absorption at doses as low as 50 g.
In Vitro StudyThe Intrinsic Factor-Vitamin B12 Receptor and Target of Teratogenic Antibodies Is a Megalin-binding Peripheral Membrane Protein with Homology to Developmental Proteins*
The 460-kDa intrinsic factor-vitamin B12 receptor, targeted by teratogenic antibodies, is a novel peripheral membrane protein with homology to developmental proteins, suggesting its potential role in fetal malformations.
In Vitro StudyHighly CitedMolecular Dissection of the Intrinsic Factor-Vitamin B12 Receptor, Cubilin, Discloses Regions Important for Membrane Association and Ligand Binding*
The N-terminal cubilin region is crucial for membrane association, while the CUB domain cluster harbors distinct sites for ligand binding in the intrinsic factor-vitamin B12 receptor.
In Vitro StudyHighly CitedImproved method for measuring vitamin B12 in serum using intrinsic factor, 57CoB12, and coated charcoal
The improved method for measuring vitamin B12 in serum using intrinsic factor, 57CoB12, and coated charcoal increases accuracy and simplifies the process.
Solid‐phase vitamin B12 assays using polyacrylamide‐bound intrinsic factor and polyacrylamide‐bound R‐binder
The new solid phase vitamin B12 assay using intrinsic factor and R-binder is simple to perform and separates serum from controls and patients with megaloblastic anaemia due to B12 deficiency.
Isolation of gastric vitamin B 12 -binding proteins using affinity chromatography. I. Purification and properties of human intrinsic factor.
Human intrinsic factor, isolated from gastric juice, effectively corrects vitamin B12 malabsorption and has a single binding site for vitamin B12.
In Vitro StudyHighly CitedEffect of the cobalt-N coordination on the cobamide recognition by the human vitamin B12 binding proteins intrinsic factor, transcobalamin and haptocorrin.
Cobamide binding to intrinsic factor and transcobalamin is strongly affected by the Co-N coordination bonds of their lower cobalt nucleotide ligands, while human haptocorrin shows distinct selectivity regarding different corrinoid structures.
In Vitro StudyHighly Cited