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Isolation and characterization of an abnormal human intrinsic factor.
J Clin Invest. 1974 May; 53(5):1274-83.JCI

Abstract

A patient has been described previously who presented at age 13 with vitamin B(12) (B(12)) deficiency secondary to a functionally abnormal intrinsic factor (IF). IF has now been isolated from the gastric juice of the patient, his sister, and both parents, who are first cousins, by using affinity chromatography on B(12)-Sepharose. Patient IF appeared normal in terms of (a) B(12) binding, (b) mol wt, (c) total amino acid and carbohydrate composition, and (d) immunodiffusion with rabbit anti-patient and anti-normal IF sera. After adsorption with normal IF, however, anti-patient IF serum precipitated the various IFs as follows: patient IF (> 95%); mother, father, and sister IF (50%); and normal IF (< 10%). Additional adsorption with mother, father, or sister IF completely inhibited the precipitation of patient IF. The association constant determined for patient IF-B(12) and human ileal mucosal homogenates (0.1 x 10(9) M(-1)) was 60-fold lower than that determined with normal IF-B(12) (6.0 x 10(9) M(-1)). Intermediate amounts of ileal IF-B(12) binding were observed with mother, father, and sister IF-B(12). These in vitro studies were supported by multiple Schilling tests, performed with a totally gastrectomized volunteer, that gave the following mean urinary excretions of [(57)Co]B(12): free B(12) (0.5%); + patient gastric juice (2.6%); + mother or father gastric juice (17%); and + normal gastric juice (26%). These studies demonstrate that the patient is homozygous and that the mother, father, and sister are heterozygous for a structurally abnormal IF that has a markedly decreased, but not absent, affinity for ileal IF-B(12) receptors. These studies also indicate that the B(12) and ileal binding sites are located on different portions of the IF molecule.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

4207620

Citation

Katz, M, et al. "Isolation and Characterization of an Abnormal Human Intrinsic Factor." The Journal of Clinical Investigation, vol. 53, no. 5, 1974, pp. 1274-83.
Katz M, Mehlman CS, Allen RH. Isolation and characterization of an abnormal human intrinsic factor. J Clin Invest. 1974;53(5):1274-83.
Katz, M., Mehlman, C. S., & Allen, R. H. (1974). Isolation and characterization of an abnormal human intrinsic factor. The Journal of Clinical Investigation, 53(5), 1274-83.
Katz M, Mehlman CS, Allen RH. Isolation and Characterization of an Abnormal Human Intrinsic Factor. J Clin Invest. 1974;53(5):1274-83. PubMed PMID: 4207620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isolation and characterization of an abnormal human intrinsic factor. AU - Katz,M, AU - Mehlman,C S, AU - Allen,R H, PY - 1974/5/1/pubmed PY - 1974/5/1/medline PY - 1974/5/1/entrez SP - 1274 EP - 83 JF - The Journal of clinical investigation JO - J Clin Invest VL - 53 IS - 5 N2 - A patient has been described previously who presented at age 13 with vitamin B(12) (B(12)) deficiency secondary to a functionally abnormal intrinsic factor (IF). IF has now been isolated from the gastric juice of the patient, his sister, and both parents, who are first cousins, by using affinity chromatography on B(12)-Sepharose. Patient IF appeared normal in terms of (a) B(12) binding, (b) mol wt, (c) total amino acid and carbohydrate composition, and (d) immunodiffusion with rabbit anti-patient and anti-normal IF sera. After adsorption with normal IF, however, anti-patient IF serum precipitated the various IFs as follows: patient IF (> 95%); mother, father, and sister IF (50%); and normal IF (< 10%). Additional adsorption with mother, father, or sister IF completely inhibited the precipitation of patient IF. The association constant determined for patient IF-B(12) and human ileal mucosal homogenates (0.1 x 10(9) M(-1)) was 60-fold lower than that determined with normal IF-B(12) (6.0 x 10(9) M(-1)). Intermediate amounts of ileal IF-B(12) binding were observed with mother, father, and sister IF-B(12). These in vitro studies were supported by multiple Schilling tests, performed with a totally gastrectomized volunteer, that gave the following mean urinary excretions of [(57)Co]B(12): free B(12) (0.5%); + patient gastric juice (2.6%); + mother or father gastric juice (17%); and + normal gastric juice (26%). These studies demonstrate that the patient is homozygous and that the mother, father, and sister are heterozygous for a structurally abnormal IF that has a markedly decreased, but not absent, affinity for ileal IF-B(12) receptors. These studies also indicate that the B(12) and ileal binding sites are located on different portions of the IF molecule. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/4207620/Isolation_and_characterization_of_an_abnormal_human_intrinsic_factor_ L2 - https://doi.org/10.1172/JCI107674 DB - PRIME DP - Unbound Medicine ER -