Vitamin B<sub>12</sub>Malabsorption Due to a Biologically Inert Intrinsic Factor

Katz, Max; Lee, Sook K.; Cooper, Bernard A.

doi:10.1056/nejm197208312870902

Cited by 75 publications

(17 citation statements)

References 22 publications

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“…This markedly reduced, but not absent, affinity for ileal receptors correlated well with a markedly reduced, but not absent, ability to stimulate Cbl absorption in a subject with a total gastrectomy. It also correlated well with the fact that the patient did not develop signs of Cbl deficiency until age (4 ,Ci/nmol), Sepharose, Cbl-Sepharose (0.7 umol/ml), purified human IF, rabbit anti-human IF, rabbit anti-hog IF, hog pepsin, and hog trypsin were obtained and prepared as described elsewhere (26,28).…”

Section: Introductionsupporting

confidence: 53%

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Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Yang¹,

Ducos²,

Rosenberg³

et al. 1985

J. Clin. Invest.

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Three siblings presented in their second year of life with megaloblastic anemia that responded to parenteral cobalamin (Cbl). Schilling tests were <1%, correcting to 5 to 15% after addition of hog intrinsic factor (IF I57CoICbl was bound to the IF before these incubations. The stabilizing effects of neutralization and Cbl were also demonstrated in vivo. Schilling tests for the siblings of 0.4, 0.5, and 1.0% increased to 2.7, 5.7, and 4.3% (P < 0.05), respectively, when the Schilling tests were repeated with the addition of NaHCO3 and cobinamide (which allows Cbl to bind immediately to IF).We conclude that Cbl malabsorption in these children is due to an abnormal IF that is markedly susceptible to acid and proteolytic enzymes which cause a decrease in its molecular weight and Cbl-binding ability and a loss of antigenic determinants that are recognized by the anti-human IF serum.

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Section: Introductionsupporting

confidence: 53%

“…A number of children have been reported (26)(27). This IF had a normal molecular weight, bound Cbl normally, and appeared to be normally resistant to alteration by acid or proteolytic enzymes.…”

Section: Introductionmentioning

confidence: 99%

Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Yang¹,

Ducos²,

Rosenberg³

et al. 1985

J. Clin. Invest.

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“…The only difference from normal which wve had in the past been able to demonstrate in the inert IF lay in its inability to facilitate B12 uptake by ileal mucosa (15). Thus, the data suggested that a specific binder of normal IF-B= was present in the Triton X-100 extract of ileal mucosa.…”

Section: Methodsmentioning

confidence: 79%

Solubilized Receptor for Intrinsic Factor-Vitamin B12 Complex from Guinea Pig Intestinal Mucosa

Katz¹,

Cooper²

1974

J. Clin. Invest.

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A B S T R A C T The absorption of vitamin B12 in many animals requires its prior association with intrinsic factor (IF) and attachment to a specific receptor in the intestine. Employing Triton X-100, we have solubilized from guinea pig ileum a factor that binds intrinsic factor-vitamin B12 complex (IF-B12). This binding factor was soluble to the extent that it was not sedimented by centrifugation at 100,000 g for 1 h and was small enough to enter the included volume of a Sepharose 4-B column.Furthermore, the ileal extract contained no microfine particles of membrane upon electron microscopic search. When a portion of the extract was incubated with a mixture of gastric juice and 6"Co-labeled vitamin B12, a portion of the radioactivity was excluded from a Sephadex G-200 column. When gastric juice from a patient with a congenital abnormality of IF that prevented its binding to intestine was substituted for normal human gastric juice, radioactivity was not excluded from the gel, indicating failure of this abnormal IF-B12 to bind to the intestinal extract. These data suggested the presence of a specific binder of IF-B12 in the ileal mucosal extract. The reactions of normal IF-B12 with the solubilized binding factor and with the membrane-bound "receptor" had several characteristics in common, including calcium dependence, temperature independence, and pH optimum near neutral. Extracts from the distal intestine showed more activity than did those from the proximal. The solubilized binding facter seemed specific for IF-B12 in that it was not blocked by prior incubation with excesses of either free vitamin B12 or IF. Binding activity of the extract was decreased by incubation at pH 2.0, by heating to 560C, and by incubation with chymotrypsin and dithiothreitol. Incubation with trypsin, neuraminidase, and sulphydryl blockers did not affect it.The Triton X-100 extract of guinea pig ileal mucosa contains a specific binding factor that probably is the

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“…The gastric IF (GIF) gene had long been postulated to be implicated in classical IFD (11)(12)(13)(14)(15), and the defect was expected ''to reflect the usual spectrum of nonsense and missense changes'' (16). In 2004, the first and hitherto sole GIF mutation was described (17).…”

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confidence: 99%

Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene

Tanner

Perko

et al. 2005

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

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Vitamin B₁₂Malabsorption Due to a Biologically Inert Intrinsic Factor

Cited by 75 publications

References 22 publications

Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Solubilized Receptor for Intrinsic Factor-Vitamin B12 Complex from Guinea Pig Intestinal Mucosa

Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene

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Vitamin B12Malabsorption Due to a Biologically Inert Intrinsic Factor

Cited by 75 publications

References 22 publications

Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis.

Solubilized Receptor for Intrinsic Factor-Vitamin B12 Complex from Guinea Pig Intestinal Mucosa

Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene

Contact Info

Product

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Vitamin B₁₂Malabsorption Due to a Biologically Inert Intrinsic Factor