Tags

Type your tag names separated by a space and hit enter

Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor.
Acta Biochim Pol. 1997; 44(4):725-33.AB

Abstract

The disease is characterised by cobalamin (Cbl) deficiency in children 0-5 years old, causing failure to thrive, infections, megaloblastic anaemia, neuropathy, and mild general malabsorption; slight proteinuria is common. Cbl injections produce remission, but Cbl malabsorption and proteinuria persist. About 250 cases have been reported. Dogs also have it. The heredity is autosomal and recessive. The physiological and pathological absorption mechanisms are described: Cbl liberated from food by digestion is first bound to haptocorrin, but in the intestine it is transferred to intrinsic factor. In the ileum the complex attaches to a receptor on the enterocytes; this requires neutral pH and Ca2+. The receptor is a membrane-bound glycoprotein consisting of multiple subunits. The receptor-ligand complex is endocytosed and degraded in lysosomes, and the vitamin is transferred to transcobalamin which carries it to tissues. The same receptor is strongly expressed in the kidneys, but urine also contains its activity which can be assayed for diagnosis. The basic lesion is an error in the ileal receptor. In the affected dogs the synthesised receptor is retained intracellularly. Urine and ileal biopsies from human cases contained little receptor but it had conserved affinity for the ligand. Recently examined Arab patients did not excrete reduced amounts of the receptor. Apparently, the disease has subsets, such as different structural errors in the receptor and possibly faulty transport inside the enterocyte. The cause of the proteinuria is unknown but kidney damage due to severe Cbl deficiency and an error in a multiligand renal receptor are among the possibilities.

Authors+Show Affiliations

Minerva Foundation Institute for Medical Research, Helsinki, Finland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

9584852

Citation

Gräsbeck, R. "Selective Cobalamin Malabsorption and the Cobalamin-intrinsic Factor Receptor." Acta Biochimica Polonica, vol. 44, no. 4, 1997, pp. 725-33.
Gräsbeck R. Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor. Acta Biochim Pol. 1997;44(4):725-33.
Gräsbeck, R. (1997). Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor. Acta Biochimica Polonica, 44(4), 725-33.
Gräsbeck R. Selective Cobalamin Malabsorption and the Cobalamin-intrinsic Factor Receptor. Acta Biochim Pol. 1997;44(4):725-33. PubMed PMID: 9584852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor. A1 - Gräsbeck,R, PY - 1997/1/1/pubmed PY - 1998/5/19/medline PY - 1997/1/1/entrez SP - 725 EP - 33 JF - Acta biochimica Polonica JO - Acta Biochim Pol VL - 44 IS - 4 N2 - The disease is characterised by cobalamin (Cbl) deficiency in children 0-5 years old, causing failure to thrive, infections, megaloblastic anaemia, neuropathy, and mild general malabsorption; slight proteinuria is common. Cbl injections produce remission, but Cbl malabsorption and proteinuria persist. About 250 cases have been reported. Dogs also have it. The heredity is autosomal and recessive. The physiological and pathological absorption mechanisms are described: Cbl liberated from food by digestion is first bound to haptocorrin, but in the intestine it is transferred to intrinsic factor. In the ileum the complex attaches to a receptor on the enterocytes; this requires neutral pH and Ca2+. The receptor is a membrane-bound glycoprotein consisting of multiple subunits. The receptor-ligand complex is endocytosed and degraded in lysosomes, and the vitamin is transferred to transcobalamin which carries it to tissues. The same receptor is strongly expressed in the kidneys, but urine also contains its activity which can be assayed for diagnosis. The basic lesion is an error in the ileal receptor. In the affected dogs the synthesised receptor is retained intracellularly. Urine and ileal biopsies from human cases contained little receptor but it had conserved affinity for the ligand. Recently examined Arab patients did not excrete reduced amounts of the receptor. Apparently, the disease has subsets, such as different structural errors in the receptor and possibly faulty transport inside the enterocyte. The cause of the proteinuria is unknown but kidney damage due to severe Cbl deficiency and an error in a multiligand renal receptor are among the possibilities. SN - 0001-527X UR - https://www.unboundmedicine.com/medline/citation/9584852/Selective_cobalamin_malabsorption_and_the_cobalamin_intrinsic_factor_receptor_ L2 - http://www.actabp.pl/pdf/4_1997/725.pdf DB - PRIME DP - Unbound Medicine ER -