Vitamin B12 Absorption and Malabsorption

Toskes, Philip P.; Deren, Julius J.

doi:10.1016/s0016-5085(19)33050-1

Cited by 63 publications

(8 citation statements)

References 136 publications

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“…The interaction of IF with this receptor has been shown to require divalent cations, is non-energy dependent and demonstrates saturation kinetics. For a review of the vitamin-B, absorptive process, the reader is referred to the reviews of Herbert (1968), Mackenzie & Donaldson (1969), Okuda (~g p ) , Toskes & Deren (1973) and Glass (1974). Early studies from this laboratory indicated that this receptor on the microvillus membrane could be solubilized (Rothenberg & Huhti, 1968).…”

supporting

confidence: 83%

Solubilization, Partial Purification and Radioassay for the Intrinsic Factor Receptor from the Ileal Mucosa

Cotter

Rothenberg

1976

Br J Haematol

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A macromolecule which binds intrinsic factor saturated with vitamin B12 has been solubilized from the guinea-pig ileum by homogenization followed by mechanical disruption without organic solvents or detergents. This intrinsic factor 'receptor' was further purified by precipitation with 30% saturated ammonium sulphate, centrifugation at 105000 g, and filtration through Sephadex G-200. Failure to precipitate the receptor following centrifugation at 105000 g for 3 h and filtration of the receptor with the included volumes through Sepharose 4B and 6B was evidence that it was solubilized. The purification of the receptor was monitored by a radiometric assay where the intrinsic factor-[57Co]vitamin-B12 complex coupled to the solubilized receptor precipitated at 15% sodium sulphate while intrinsic factor-[57Co]B12 alone remained soluble at this salt concentration. This radioassay also permitted the in vitro study of the interaction of the solubilized receptor and intrinsic factor saturated with [57Co]B12. The receptor did not bind intrinsic factor-[57Co]B12 below pH 5 while binding was observed to pH 9.0. Binding was equivalent at 37 degrees C and 25 degrees C, but was markedly reduced at 4 degrees C and 56 degrees C and was destroyed at 100 degrees C. The receptor resisted 60 min of digestion by trypsin, chymotrypsin, pronase and subtilisin. After 180 min digestion, pronase and subtilisin inactivated 90% and 41% of the receptor respectively, whereas trypsin and chymotrypsin inactivated only 21% and 23%. Trisodium EDTA inhibited the binding of intrinsic factor-[57Co]B12 to the receptor and this inhibition could be reversed by the addition of excess Ca2+. Mg2+ and Mn2+ were less effective than Ca2+ for the activity of the receptor. Kinetic analysis of the reaction indicated a maximum velocity of 0.083 nmole IF bound B12/min with a Km of 1.36 x 10(-10) M. The solubilized receptor had a greater affinity for intrinsic factor bound to vitamin B12 than for intrinsic factor free of vitamin B12. The solubilization of this intrinsic factor receptor without chemicals suggests that it is not an integral component of the microvillus membranes hydrophobically bonded to the lipid matrix, but rather a peripheral protein weakly associated with the membrane by non-covalent interaction.

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supporting

confidence: 83%

Solubilization, Partial Purification and Radioassay for the Intrinsic Factor Receptor from the Ileal Mucosa

Cotter

Rothenberg

1976

Br J Haematol

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“…Malabsorption of vitamin B 12 has been observed in 30–50% of adult patients with pancreatic exocrine insufficiency 153–155 . Vitamin B 12 malabsorption occurs in pancreatic insufficiency due to the impaired degradation of R‐proteins bound to dietary vitamin B 12 156–158 .…”

Section: Dual‐label Schilling Testmentioning

confidence: 99%

Pancreatic function testing

Chowdhury

Forsmark

2003

Aliment Pharmacol Ther

190

122

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SUMMARYPancreatic function tests are most commonly used to diagnose chronic pancreatitis. These tests include tests which document exocrine or endocrine gland insufficiency and tests which instead measure gradations of decreased secretory capacity. The tests in the former category generally become abnormal when advanced, longstanding chronic pancreatitis is present. Tests in the latter category, however, have the potential to detect chronic pancreatitis at an earlier stage than other available diagnostic tests, including commonly used imaging tests such as computed tomography and endoscopic retrograde cholangiopancreatography. This potential advantage of diagnostic sensitivity is, however, counterweighed by the fact that these tests which measure stimulated secretory capacity are only available at a very few referral centres. This article will review the variety of pancreatic function tests and describe their rationale, accuracy, cost, and clinical usefulness.

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“…However, each of these notions has not withstood the test of repetitive or experimental confirmation (Veeger et al, 1962;Toskes et al, 1971;Toskes & Deren, 1972). Furthermore, previous (Cheney, 1936) and more recent reports (Toskes et al, 1971) speculated that the pancreatic juice is endowed with intrinsic-factor activity, or that an endogenic binder able to bind the intrinsic-factor-vitamin B12 complex converts the complex into a non-absorbable form (Toskes & Deren, 1973) (see also the Discussion section).…”

mentioning

confidence: 99%

Comparative studies on intrinsic factor and cobalophilin in different parts of the gastrointestinal tract of the pig

Marcoullis

Merivuori

Gräsbeck

1978

Biochemical Journal

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The vitamin B(12) binders in the pig pyloric mucosa gastric and intestinal juice from the upper gastrointestinal tract were fractionated into only two molecular forms, classified as intrinsic factor and cobalophilin. The unsaturated vitamin B(12)-binding power due to cobalophilin was lower in the intestinal than in the gastric juice. Electrofocusing revealed that intrinsic factor and cobalophilin in the intestinal juice contained more of the ;neutral'-type isoproteins, and the suggestion is made that this is due to enzyme activity. The gastric-juice intrinsic factor contained more acidic isoproteins, which supports the hypothesis that carbohydrate is added on to the polypeptide chain of this protein before it is secreted into gastric juice. The gastric- and intestinal-juice cobalophilins, studied also by electrofocusing, differed from that of pyloric mucosa and they appeared to be of salivary origin. With regard to molecular dimensions there was no significant difference between the intrinsic factors and cobalophilins from all sources studied. All cobalophilins had molecular weights by the formula of Svedberg of approx. 92500, Stokes radii of 4.62nm and sedimentation coefficients of 5.15S. The corresponding values for the intrinsic factors were 63600, 3.57nm and 4.38S. In addition, the intrinsic factors exhibited similar avidities for binding to the solubilized ileal intrinsic-factor receptor. Also the intrinsic factors and cobalophilins, irrespective of their source, bound to the analogous specific xenoantibodies with the same avidity. The present results demonstrate that intrinsic factor remains practically unaltered during its passage through the proximal intestine and render unlikely the speculations made about the presence of an endogenous binder for intrinsic factor as well as the existence of a ;pancreatic intrinsic factor'. In addition, they are compatible with the theory that the interference by undegraded cobalophilin may be the reason for the abnormal vitamin B(12) absorption observed in patients with pancreatic insufficiency.

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Vitamin B12 Absorption and Malabsorption

Cited by 63 publications

References 136 publications

Solubilization, Partial Purification and Radioassay for the Intrinsic Factor Receptor from the Ileal Mucosa

Solubilization, Partial Purification and Radioassay for the Intrinsic Factor Receptor from the Ileal Mucosa

Pancreatic function testing

Comparative studies on intrinsic factor and cobalophilin in different parts of the gastrointestinal tract of the pig

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