scholarly journals Selective cobalamin malabsorption and the cobalamin-intrinsic factor receptor.

1997 ◽  
Vol 44 (4) ◽  
pp. 725-733 ◽  
Author(s):  
R Gräsbeck
Keyword(s):  
Intrinsic Factor ◽  
Failure To Thrive ◽  
Megaloblastic Anaemia ◽  
Kidney Damage ◽  
Ligand Complex ◽  
Receptor Ligand ◽  
Neutral Ph ◽  
Renal Receptor ◽  
Membrane Bound ◽  
Cobalamin Malabsorption

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.

scholarly journals Defective brush-border expression of intrinsic factor-cobalamin receptor in canine inherited intestinal cobalamin malabsorption

1991 ◽  
Vol 266 (7) ◽  
pp. 4489-4494
Author(s):  
J C Fyfe ◽  
K S Ramanujam ◽  
K Ramaswamy ◽  
D F Patterson ◽  
B Seetharam
Keyword(s):  
Brush Border ◽  
Intrinsic Factor ◽  
Cobalamin Malabsorption

Molecular Characterization of the Receptor−Ligand Complex for Parathyroid Hormone†

Biochemistry ◽  
1999 ◽  
Vol 38 (20) ◽  
pp. 6397-6405 ◽  
Author(s):  
Christian Rölz ◽  
Maria Pellegrini ◽  
Dale F. Mierke
Keyword(s):  
Parathyroid Hormone ◽  
Molecular Characterization ◽  
Ligand Complex ◽  
Receptor Ligand

Preparation of Target CETP in Docking-Based Virtual Screening

2013 ◽  
Vol 477-478 ◽  
pp. 1495-1498
Author(s):  
Wei Ye Tao ◽  
Lai You Wang ◽  
Guo Quan Huang ◽  
Man Luo
Keyword(s):  
Crystal Structure ◽  
Virtual Screening ◽  
Cholesteryl Ester ◽  
Active Site ◽  
Target Protein ◽  
Drug Molecule ◽  
Ligand Complex ◽  
Receptor Ligand ◽  
Strong Repulsion

When conducting docking-based virtual screening, we should carefully prepare the target protein. Generally, the ligands coupled with the receptor-ligand complex are often deleted from the crystal structure, but it is unknown that in which situation the ligands should be deleted. Taking CETP for example, this study conducted virtual screening against CETP through 2 different styles. In style 1, the cholesteryl ester near the active site was deleted. In style 2, the cholesteryl ester was kept to conduct the virtual screening. We found that the results were very different from each other and style 2 was the preferable choice in this situation. The reason why like this is that there is strong repulsion between drug molecule and the cholesteryl ester.

Soluble neutral maltase–glucoamylase from the small intestine: separation and characterization of components with differing affinity for concanavalin A

1982 ◽  
Vol 60 (11) ◽  
pp. 1007-1013 ◽  
Author(s):  
G. Forstner ◽  
A. Salvatore ◽  
L. Lee ◽  
J. Forstner
Keyword(s):  
Concanavalin A ◽  
Gradient Elution ◽  
Soluble Form ◽  
Rat Intestine ◽  
Ph Optimum ◽  
Molecular Weights ◽  
Neutral Ph ◽  
Membrane Bound ◽  
Sepharose 4B

Intestinal maltase with a neutral pH optimum exists in both a brush border membrane-bound form and a soluble form in suckling rat intestine. Previous experiments in our laboratory have shown that the soluble enzyme contains a component which binds much more tightly to concanavalin A (ConA) than solubilized forms of the membrane enzyme. We studied the origin of this component by subjecting neutral, soluble maltase activity to chromatography on Sepharose 4B at age 13, 18 (preweaning), and 25 (postweaning) days. At 13 days, two maltase peaks were obtained with approximate molecular weights of 400 000 (peak I) and 150 000 (peak II). Peak II was less prominent at 18 days and was absent at 25 days. At 13 days, the majority of peak I consisted of material which was bound between 0.025 and 0.05 M α-methyl mannoside on gradient elution chromatography of ConA-Sepharose. Peak II contained material which eluted between 0.075 and 0.3 M α-methyl mannoside. At 25 days, all of the soluble maltase eluted between 0.025 and 0.04 M α-methyl mannoside. Peak I and peak II maltases had similar pH optima and Km's for maltase. Peak II maltase had a fourfold greater activity toward glycogen than peak I maltase with approximately the same activity for palatinose, turanose, and trehalose. Both maltases were precipitated by an antibody raised against adult membrane-bound maltase. Soluble maltase with neutral pH activity in the suckling rat intestine, therefore, consists of two immunologically related isozymes which differ in their molecular weight, their binding by ConA, and their specificity for glycogen. The small isozyme disappears at or about the time of weaning.

Chemoattractant-induced NADPH oxidase activity in human monocytes is terminated without any association of receptor-ligand complex to cytoskeleton

Inflammation ◽  
1995 ◽  
Vol 19 (2) ◽  
pp. 179-191 ◽  
Author(s):  
Agneta Johansson ◽  
Eva S�rndahl ◽  
Tommy Andersson ◽  
Torbj�rn Bengtsson ◽  
Helen Lundqvist ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Human Monocytes ◽  
Ligand Complex ◽  
Receptor Ligand ◽  
Nadph Oxidase Activity

scholarly journals Demyelinating lesions as a presenting feature of pernicious anaemia: Case report and literature review

2017 ◽  
Vol 4 (3) ◽  
pp. 7
Author(s):  
Rahul Daimari ◽  
Anthony A Oyekunle ◽  
Cassandra A Ocampo ◽  
Lawrence Kwape
Keyword(s):  
Clinical Features ◽  
Clinical Laboratory ◽  
Intrinsic Factor ◽  
Pernicious Anaemia ◽  
Neurological Impairment ◽  
Megaloblastic Anaemia ◽  
Cobalamin Deficiency ◽  
Female Population ◽  
Radiologic Findings ◽  
Demyelinating Lesions

Background: Pernicious anaemia (PA) describes megaloblastic anaemia resulting from cobalamin deficiency that is due to the absence of intrinsic factor (IF). Most cases are autoimmune in origin, with antibodies to parietal cells, IF or the cobalamin – IF complex.Methods: We report the clinical features, investigation and treatment of a patient in whom the first presentation of PA was demyelinating brain lesions. She presented with clinical features initially of neurological impairment and subsequently anaemia. Imaging studies were consistent with demyelinating lesions extending from the cortex to the midbrain. Peripheral blood and bone marrow findings were consistent with megaloblastic anaemia, which were confirmed by subnormal serum cobalamin levels. The patient was treated with parenteral cobalamin and oral folic acid.Results: She responded with complete resolution of anaemia and complete clinical neurological response.Conclusion: Clinical, laboratory and radiologic findings are important in the screening of patients presenting with demyelinating lesions, as these may help in the diagnosis of rare cases of PA. These tests are just as relevant even in the young African female population.

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