Transfer of cobalamin from intrinsic factor to transcobalamin II

Brada, Nancy; Gordon, M. M.; Wen, Jipu; Alpers, David H.

doi:10.1016/s0955-2863(00)00129-7

Cited by 18 publications

(17 citation statements)

References 27 publications

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“…However, the absence of a His coordination bond and wide binding site in IF might allow Cbl to move in and out of IF freely compared with TC. In fact, Cbl can transfer at a low rate from IF to TC at neutral pH, but not from TC to IF (27).…”

Section: Resultsmentioning

confidence: 93%

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Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

Mathews¹,

Gordon

Chen³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-Å resolution. The overall fold of the molecule is that of an ␣6/␣6 barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an ␣-and a ␤-domain and one Cbl, and two truncated molecules with only an ␣-domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co 2؉ is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.5] is a water-soluble vitamin and is essential for the growth and development of all mammals, including humans. Cbl is a member of the corrinoid series of cobalt-containing compounds and is distinguished from some other members of this group by possessing a nucleotide side chain terminating in dimethylbenzimidazole (1, 2). It serves as a key enzymatic cofactor for a number of methyltransferase and mutase reactions occurring in nature (3). In mammals, it contributes the prosthetic group for two important enzymes, methionine synthase (a methyltransferase) and methylmalonylCoA mutase (1, 2, 4).In mammals, three proteins are involved in the uptake, transport, and storage of Cbl. These are gastric intrinsic factor (IF), trans-Cbl II (TC), and haptocorrin (HC). These are immunologically distinct proteins with a protein core of Ϸ46 kDa. IF and HC are heavily glycosylated, but TC is not (5, 6). In humans, the genes for IF and HC are located in chromosome 22 (7,8), whereas the gene for TC is located in chromosome 11 (9). Human IF contains 399-aa residues plus Ϸ15% carbohydrate, giving it a molecular mass of Ϸ60 kDa, as observed by gel filtration (10-13). All three proteins promote Cbl entry through endocytosis involving distinct cell surface receptors (5,(14)(15)(16)(17)(18)(19)(20).Dietary Cbl is bound first to HC in the gastric lumen but is transferred to IF in the duodenum after degradation of HC by pancreatic proteases. IF is responsible for transit of Cbl through the small intestine and delivery of it to the endothelial cells that line the ileum. The IF-Cbl complex is then recognized by the IF-Cbl receptor, cubilin (CUB), located on the luminal side of the intestinal mucosal cells, and mediates its internalization. Lysosomal degradation of the internalized IF-Cbl complex releases Cbl, which is then able to bind to TC, probably within the enterocyte. The TC-Cbl complex is then translocated across the basolateral membrane and released into the circulation, to be taken up by TC-Cbl receptor-mediated process by all cells in the body. Lysosomal dissociation of the complex then occurs along with transfer of Cbl to the coenzyme methyl-and Ado-Cbl in the cytoplasm and i...

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Section: Resultsmentioning

confidence: 93%

“…It has been speculated that intracellular transfer of Cbl from IF to TC could occur in a neutral cellular compartment, because Cbl-binding affinity decreases rapidly with decrease in pH (27). The crystals of IF, human TC, and bovine TC were grown at pH 6, 7.5, and 8.5, respectively.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

Mathews¹,

Gordon

Chen³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…A culture of KM71 cells with the TCII gene from human small intestine was expressed in BMGY and BMMY media (7,11). Production of rhTCII decreased 48 h after induction, and the protein was harvested prior to this time.…”

Section: Methodsmentioning

confidence: 99%

Equilibrium and Kinetic Analyses of the Interactions between Vitamin B12 Binding Proteins and Cobalamins by Surface Plasmon Resonance

Cannon

Myszka

Bagnato

et al. 2002

Analytical Biochemistry

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“…Vitamin B 12 is released from the gut epithelial cells as a complex bound to a 38-kDa protein called transcobalamin II (TC-II). This process of absorption across the gut epithelium takes about 3 to 4 hours [25]. The 460-kDa IF receptor (cubulin) is also expressed in the kidney and in the yolk sac of animals [26].…”

Section: Absorption Transport and Bioavailabilitymentioning

confidence: 99%

Folate and Vitamin B₁₂ Metabolism: Overview and Interaction with Riboflavin, Vitamin B₆, and Polymorphisms

Shane¹

2008

Food Nutr Bull

125

130

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Transfer of cobalamin from intrinsic factor to transcobalamin II

Cited by 18 publications

References 27 publications

Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

Equilibrium and Kinetic Analyses of the Interactions between Vitamin B12 Binding Proteins and Cobalamins by Surface Plasmon Resonance

Folate and Vitamin B₁₂ Metabolism: Overview and Interaction with Riboflavin, Vitamin B₆, and Polymorphisms

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Transfer of cobalamin from intrinsic factor to transcobalamin II

Cited by 18 publications

References 27 publications

Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

Equilibrium and Kinetic Analyses of the Interactions between Vitamin B12 Binding Proteins and Cobalamins by Surface Plasmon Resonance

Folate and Vitamin B12 Metabolism: Overview and Interaction with Riboflavin, Vitamin B6, and Polymorphisms

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Product

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Folate and Vitamin B₁₂ Metabolism: Overview and Interaction with Riboflavin, Vitamin B₆, and Polymorphisms