Vitamin b12 absorption mechanisms
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Vitamin B12 Absorption Mechanisms: Key Proteins and Pathways
Role of Intrinsic Factor and Carrier Proteins in Vitamin B12 Absorption
Vitamin B12 absorption in mammals is a complex process that relies heavily on specific proteins and receptors. The most important of these is intrinsic factor, a protein produced by the stomach’s parietal cells. Intrinsic factor binds to vitamin B12 in the stomach and is essential for its efficient absorption in the small intestine, specifically the ileum. This binding allows vitamin B12 to be recognized and internalized by a receptor complex made up of Cubilin (Cubn) and Amnionless (Amn) on the surface of ileal cells, ensuring the vitamin is absorbed into the body 234.
Other carrier proteins, such as haptocorrin and transcobalamin, also play roles in the transport and cellular uptake of vitamin B12. Haptocorrin binds vitamin B12 in the saliva and stomach, protecting it from stomach acid, while transcobalamin is responsible for transporting vitamin B12 in the bloodstream to various tissues 29.
Active and Passive Absorption Pathways
There are two main mechanisms for vitamin B12 absorption: active and passive. The active mechanism is highly efficient but saturable, relying on intrinsic factor and specific receptors in the ileum. This pathway can absorb only a limited amount of vitamin B12 at a time, with a maximum capacity of about 1.2–2.5 micrograms per dose. At higher doses, a small fraction of vitamin B12 can be absorbed passively across the gut lining, but this process is very inefficient, accounting for less than 1% of the dose 38.
Cellular Uptake and Reabsorption
After absorption in the intestine, vitamin B12 is transported in the blood bound to transcobalamin and taken up by cells through the CD320 receptor. CD320 is found on the surface of many cell types, including those in the intestine and kidney, and is crucial for the cellular uptake and reabsorption of vitamin B12. Proper targeting of CD320 to the cell membrane is essential for efficient vitamin B12 metabolism, and disruptions in this process can lead to deficiency 26.
Special Considerations in Infants and After Gastrectomy
In infants, the mechanisms for vitamin B12 absorption are not fully mature. Early in life, haptocorrin from human milk may help mediate vitamin B12 absorption until the infant’s own intrinsic factor system develops. As infants grow, intrinsic factor becomes the primary mediator of vitamin B12 absorption 57.
After gastrectomy (removal of the stomach), the production of intrinsic factor is lost, leading to rapid development of vitamin B12 deficiency unless supplementation is provided. This highlights the critical role of intrinsic factor in the absorption and reabsorption of vitamin B12 34.
Genetic and Acquired Disorders Affecting Absorption
Disorders that affect the production or function of intrinsic factor, or the receptors involved in vitamin B12 uptake, can lead to deficiency. These include inherited conditions like Imerslund-Gräsbeck syndrome and rare intrinsic factor deficiencies, as well as acquired conditions such as pernicious anemia and age-related malabsorption 24.
Conclusion
Vitamin B12 absorption is a highly regulated process involving intrinsic factor, specific carrier proteins, and membrane receptors. The active absorption pathway is efficient but easily saturated, while passive absorption plays a minor role at high doses. Disruptions in any part of this system—whether due to genetic, developmental, or acquired factors—can lead to vitamin B12 deficiency, underlining the importance of these mechanisms for health 2346789.
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