Comprehensive Physiology Wiley Online Library

Gastric Intrinsic Factor and Cobalamin Absorption

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Abstract

The sections in this article are:

1 Types of Cobalamin
2 Dietary Sources and Requirements
3 Biological Reactions and Deficiency Manifestations
4 Cobalamin‐Binding Proteins
4.1 Definition
4.2 Specifity of Structure and Binding
4.3 Site of Production, Synthesis, and Secretion
4.4 Structure, Function, and Congenital Abnormalities
5 Intestinal Absorption of Cobalamin
5.1 Gastric Phase
5.2 Intestinal Luminal Phase
5.3 Mucosal Phase
5.4 Studies on Ileal Receptor
5.5 Passive Absorption and Absorption in Neonatal Period
5.6 Uptake and Fate of Intrinsic Factor
5.7 Measurement of Cobalamin Absorption and Body Stores
6 Disorders of Cobalamin Absorption
Figure 1. Figure 1.

Cobalamin structure. X, variable ligands. R, R′, acetamide and propionamide chains located on periphery of corrin ring.

[From Seetharam and Alpers 187.]
Figure 2. Figure 2.

Enzyme defects in intracellular utilization of cobalamin (cbl).

Figure 3. Figure 3.

Human parietal cell, anti‐intrinsic factor (IF). Reaction product visible on tubulovesicles (black arrows) and multivesicular bodies (white arrows). IF is present on rough endoplasmic reticulum and perinuclear envelope but is not clearly visible at this magnification. Blunt microvilli and chief cell are not stained. N, nucleus; RER, endoplasmic reticulum; G, Golgi apparatus; C, chief cells. × 12,000.

[From Levine et al. 129.]
Figure 4. Figure 4.

A: electron micrograph of parietal cells in biopsy from basal period reacted with antihuman IF. IF is located on rough endoplasmic reticulum (small arrow) and golgi (white arrow). × 50,000. Bar, 0.2 μm. B: details of canalicular lumen from 15‐min poststimulation biopsy, reacted with anti‐human IF. Multiple microvilli with IF on surface membrane but also cross‐sectioned microvillus (arrow) with “doughnut” appearance and IF on both inner and outer membranes. × 50,000. Bar, 0.2 μm.

[From Levine et al. 130.]
Figure 5. Figure 5.

Proposed scheme for utilization of dietary cbl.

[From Seetharam and Alpers 187.]
Figure 6. Figure 6.

Electron micrographs of villus tip region from dog ileum that has been reacted with anti‐IF‐cobalamin receptor. At this level immunoreactive receptor is present in majority of microvillus pits (black arrowheads), in vesicles (V) between nucleus (N) and surface, and rough endoplasmic reticulum (curved black arrows, inset). In addition, villus tip enterocytes also demonstrate receptor in multivesicular bodies (circled in black) and in membranous envelopes surrounding nuclei (N) (shown at higher power in inset, curved white arrows). Receptor is not seen in basolateral membrane. Bars, 1 μm, × 9,800; 0.5 μm, × 20,000 (inset).

[From Levine et al. 128.]
Figure 7. Figure 7.

Possible pathways for movement of IF and cbl within enterocyte. Established pathways are marked by solid lines. Pathways that are incompletely established or proposed are marked by broken lines.

[From Seetharam and Alpers 188.]
Figure 8. Figure 8.

Effect of trypsin (20 mg) and nonradioactive cbl analogue (100 nmol) on absorption of 0.4 nmol of [57Co]cbl in patients with pancreatic insufficiency as measured by Schilling tests. Trypsin and analogues were mixed with [57Co]cbl and incubated for 15 min at 4°C before oral administration. Schilling tests were performed in order from left to right.

[From Allen et al. 8.]


Figure 1.

Cobalamin structure. X, variable ligands. R, R′, acetamide and propionamide chains located on periphery of corrin ring.

[From Seetharam and Alpers 187.]


Figure 2.

Enzyme defects in intracellular utilization of cobalamin (cbl).



Figure 3.

Human parietal cell, anti‐intrinsic factor (IF). Reaction product visible on tubulovesicles (black arrows) and multivesicular bodies (white arrows). IF is present on rough endoplasmic reticulum and perinuclear envelope but is not clearly visible at this magnification. Blunt microvilli and chief cell are not stained. N, nucleus; RER, endoplasmic reticulum; G, Golgi apparatus; C, chief cells. × 12,000.

[From Levine et al. 129.]


Figure 4.

A: electron micrograph of parietal cells in biopsy from basal period reacted with antihuman IF. IF is located on rough endoplasmic reticulum (small arrow) and golgi (white arrow). × 50,000. Bar, 0.2 μm. B: details of canalicular lumen from 15‐min poststimulation biopsy, reacted with anti‐human IF. Multiple microvilli with IF on surface membrane but also cross‐sectioned microvillus (arrow) with “doughnut” appearance and IF on both inner and outer membranes. × 50,000. Bar, 0.2 μm.

[From Levine et al. 130.]


Figure 5.

Proposed scheme for utilization of dietary cbl.

[From Seetharam and Alpers 187.]


Figure 6.

Electron micrographs of villus tip region from dog ileum that has been reacted with anti‐IF‐cobalamin receptor. At this level immunoreactive receptor is present in majority of microvillus pits (black arrowheads), in vesicles (V) between nucleus (N) and surface, and rough endoplasmic reticulum (curved black arrows, inset). In addition, villus tip enterocytes also demonstrate receptor in multivesicular bodies (circled in black) and in membranous envelopes surrounding nuclei (N) (shown at higher power in inset, curved white arrows). Receptor is not seen in basolateral membrane. Bars, 1 μm, × 9,800; 0.5 μm, × 20,000 (inset).

[From Levine et al. 128.]


Figure 7.

Possible pathways for movement of IF and cbl within enterocyte. Established pathways are marked by solid lines. Pathways that are incompletely established or proposed are marked by broken lines.

[From Seetharam and Alpers 188.]


Figure 8.

Effect of trypsin (20 mg) and nonradioactive cbl analogue (100 nmol) on absorption of 0.4 nmol of [57Co]cbl in patients with pancreatic insufficiency as measured by Schilling tests. Trypsin and analogues were mixed with [57Co]cbl and incubated for 15 min at 4°C before oral administration. Schilling tests were performed in order from left to right.

[From Allen et al. 8.]
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How to Cite

Bellur Seetharam, David H. Alpers. Gastric Intrinsic Factor and Cobalamin Absorption. Compr Physiol 2011, Supplement 19: Handbook of Physiology, The Gastrointestinal System, Intestinal Absorption and Secretion: 437-461. First published in print 1991. doi: 10.1002/cphy.cp060420