Studies on the Role of Intrinsic Factor in Vitamin B12 Absorption, Transport, and Storage

1959 ◽  
Vol 7 (4) ◽  
pp. 433-443 ◽  
Author(s):  
VICTOR HERBERT
2020 ◽  
Vol 27 (19) ◽  
pp. 3123-3150 ◽  
Author(s):  
Renata Kozyraki ◽  
Olivier Cases

Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.


Gut ◽  
1973 ◽  
Vol 14 (1) ◽  
pp. 13-19 ◽  
Author(s):  
R. G. Strickland ◽  
J. M. Fisher ◽  
K. Lewin ◽  
K. B. Taylor

Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 747-753 ◽  
Author(s):  
H. G. Desai ◽  
F. P. Antia

Abstract Sixteen patients (from Bombay) with severe vitamin B12 malabsorption due to intrinsic factor deficiency, presenting as subacute combined degeneration of the cord (7), tropical sprue (3), anemia (2), thyrotoxicosis (2), diabetes mellitus (1), and pain in the abdomen (1), are reported. The difficulties of establishing a definite diagnosis of pernicious anemia in Indian population are described. The lower incidence of circulating intrinsic factor antibody (IFA) in Indian patients with histamine-fast achlorhydria and poor vitamin B12 absorption is emphasized. The necessity of separating atrophic gastritis, with severely impaired vitamm B12 absorption, from pernicious anemia on the basis of absence or presence of IFA in serum and/or gastric juice cannot be overemphasized.


1965 ◽  
Vol 208 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Kunio Okuda ◽  
Katsumi Sasayama

Evidence is presented that intrinsic-factor (IF) activity is present in the small intestine as far down as the ileal end. Physiologic doses of radioactive vitamin B12 without IF were applied directly into various levels of the intestine by surgical and other means in man and rats, and significant absorption was obtained from the small intestine. Absorption inhibition by ethylenediaminetetraacetate and its counteraction by Ca ion demonstrated that such absorption was dependent on IF action. The large intestine was shown to be incapable of physiologic absorption of vitamin B12, and IF was totally ineffective. It is proposed that physiologically, gastric IF descends with some activity in the small intestine, where more of the food vitamin B12 is liberated by digestion and subjected to IF.


Science ◽  
1957 ◽  
Vol 126 (3273) ◽  
pp. 558-558 ◽  
Author(s):  
J. ABELS ◽  
M. G. WOLDRING ◽  
J. J. M. VEGTER ◽  
H. O. NIEWEG

Blood ◽  
1970 ◽  
Vol 36 (1) ◽  
pp. 20-27 ◽  
Author(s):  
W. J. IRVINE ◽  
D. R. CULLEN ◽  
LAURA SCARTH ◽  
J. D. SIMPSON ◽  
S. H. DAVIES

Abstract The absorption of 58Co-vitamin B12 was assessed by the method of total body counting in 25 patients with frank P.A., five with latent P.A., 47 with achlorhydria but without malabsorption of vitamin B12 and 47 acid-secreting patients. A total of 192 tests was done. With or without prior stimulation of intrinsic factor secretion by pentagastrin the upper level of absorption of vitamin B12 in patients with frank or latent P.A. was 25 per cent. Taking an equivocal result to be 21-25 per cent inclusive, the total body counting method was able to distinguish P.A. patients from those with achlorhydria without P.A. with 87 per cent accuracy and one per cent error and from non-P.A. achlorhydric patients and acid secretors combined with 91 per cent accuracy and 0.5 per cent error. Pentagastrin stimulation did not improve the separation between achlorhydric patients with and without P.A. but raised the lower limit of retention of vitamin B12 from 24 to 44 per cent in the acid secreting patients. The method of total body counting is recommended as a method of assessing vitamin B12 absorption.


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