Vitamin B12, or cobalamin, is a water-soluble vitamin necessary for nerve cell function, red blood cell formation, and DNA synthesis. The human body cannot produce B12, making it dependent on external sources. Its journey from food to individual cells involves a multi-stage pathway of digestion, absorption, and transport.
The Journey from Food to the Small Intestine
Vitamin B12 is present in animal-based foods like meat, fish, eggs, and dairy products. In these sources, B12 is attached to proteins and must be separated before the body can use it. This process begins in the stomach, where hydrochloric acid and the enzyme pepsin work to sever the bond between B12 and its protein.
Once freed, the vitamin is bound by a protective protein called haptocorrin (or R-protein), found in saliva and gastric fluids. Haptocorrin shields the B12 molecule from the stomach’s acidic environment. At the same time, parietal cells in the stomach lining secrete intrinsic factor (IF). Intrinsic factor does not yet interact with B12, which remains bound to haptocorrin as it moves into the small intestine.
Absorption in the Small Intestine
The B12-haptocorrin complex travels from the stomach into the duodenum, the first section of the small intestine. In this less acidic environment, pancreatic enzymes called proteases break down the haptocorrin. This action releases vitamin B12, leaving it free to bind with intrinsic factor.
This new B12-intrinsic factor (B12-IF) complex travels to the ileum, the final segment of the small intestine. Cells lining the ileum have specific receptors, known as cubam receptors, that recognize and bind to the B12-IF complex. The receptor internalizes the complex, allowing B12 to pass through the intestinal wall into circulation. This receptor-mediated process is the primary mechanism for B12 absorption.
Transport and Cellular Entry
Once the B12-IF complex is absorbed into the ileum’s cells, it is broken apart. The intrinsic factor is degraded, and the vitamin B12 is handed off to a new carrier protein, transcobalamin II (TCII). This B12-TCII complex then exits the intestinal cells and enters the bloodstream.
The B12-TCII complex transports the vitamin to various tissues. About half of the absorbed B12 goes to the liver for storage, while the rest is distributed to areas like the bone marrow. Cells in these tissues have surface receptors that recognize transcobalamin II, allowing them to pull the complex from the blood and bring the vitamin inside.
Cellular Functions of B12
Once inside a cell, vitamin B12 acts as a cofactor for two enzymes that facilitate metabolic reactions. It is converted into its active forms, methylcobalamin and adenosylcobalamin, within the cell. These different forms are required for separate, but equally important, cellular processes.
One of these enzymes, methionine synthase, is located in the cell’s cytoplasm and requires methylcobalamin. It helps convert an amino acid called homocysteine into another amino acid, methionine. Methionine is used to produce proteins and is a source for DNA methylation, a process necessary for DNA synthesis. This pathway is linked with the folate cycle and is directly related to the production of healthy red blood cells.
The second enzyme, methylmalonyl-CoA mutase, operates inside the mitochondria and uses adenosylcobalamin. This enzyme is part of a pathway that metabolizes fats and proteins, converting methylmalonyl-CoA into succinyl-CoA to generate energy. This process is important for maintaining the myelin sheath, the protective layer insulating nerve cells. A failure in this conversion can damage myelin and contribute to neurological problems.
Disruptions to the B12 Pathway
Breakdowns in the B12 absorption pathway can lead to a deficiency. In the stomach, low stomach acid from conditions like atrophic gastritis or acid-suppressing medications can prevent B12 from being released from food. Pernicious anemia is an autoimmune disorder where the immune system attacks the parietal cells that produce intrinsic factor or the factor itself, impairing absorption.
Pancreatic issues can also interfere with B12 absorption. If the pancreas does not produce enough digestive enzymes, haptocorrin may not be broken down in the small intestine. This prevents B12 from binding to intrinsic factor and can occur in cases of pancreatic insufficiency.
Problems within the small intestine are another cause of deficiency. Diseases like Crohn’s or celiac disease can damage the lining of the ileum, impairing absorption. Surgical removal of the ileum also eliminates the body’s ability to absorb B12. Since B12 is found almost exclusively in animal products, a strict vegan or vegetarian diet without fortified foods or supplements will lead to a deficiency.