Utilization of vitamin B12
Because vitamin B12 has the largest and, probably, the most complicated molecule of any of the water-soluble nutrients, it is not surprising that its deficiency is caused more frequently by problems of absorption than by dietary inadequacy. Of equal interest is the fact that its active absorption requires the presence in the gastric secretions of an even larger molecule, a glycoprotein called Castle's intrinsic factor (IF), which is produced by the parietal cells of the gastric mucosa. The Bi2-IF complex forms in the stomach and passes through the upper part of the small intestine to the ileum, where the IF attaches itself to the epithelial cells specific to this area of the gu t and thereby facilitates the transfer of vitamin BI2 into the ileal epithelium. Calcium and luminal pH above 6 are also necessary for this transfer. Because the IF is not found in lymph or plasma, it is presumed to remain in the intestinal tract.
The BI2-IF complex is stable against proteolytic degradation in the intestine, whereas gastric and intestinal hydrolysis of food proteins that bind BI2 is essential for its release before it forms a complex with the IF and thereby makes the vitamin available to the body.
Passive absorption by simple diffusion can account for a limited amount (1% to 3%) of absorption. This is inadequate from normal dietary intake ofvitamin B12, but in the absence ofIF, permits the effective oral administration oflarge doses of vitamin B12. However, intramuscular administra tion of the vitamin is the more common mode of treatment.
When cobalamin is released into the bloodstream, it is a ttached to another protein (transcobalamin ll) and carried to the various tissues. Protein-bound vitamin BI2 not immediately needed is stored in the liver (mainly as adenosylcobalamin), which is capable of storing relatively large amounts of this nutrient. As the quantity of the vitamin increases in the diet, the percentage absorbed decreases.
The major form of vitamin BI2 in serum is methylcobalamin. Normal serum levels of vitamin BI2 range from 200 to 700 picograms (1 pg = 10-12 g) per ml.
In addition to transcobalamin II (TCll), at least two other serum proteins bind vitamin B12, known as TCI and TCn!. Most of the total Bl2-binding capacity is as TCll, which is believed to be the source of BI2 to the tissues. Cellular uptake ofBI2 from TCII requires a receptor mechanism similar to the ileal uptake of the vitamin and is calcium and pH dependent. The functions of the other transcobalamins are not known; BI2 bound to TCI has a long turnover time and, therefore, has been suggested to represent a circulating storage form of the vitamin. Both TCI and TCII are glycoproteins and are also known as Rproteins or cobalophilins, whereas TCII contains only amino acids.
The storage of vitamin BI2 in the liver, its enterohepatic circulation, and lack of significant catabolism in the body contribute to the efficient utilization ofthis vitamin in healthy people. Deficiency symptoms can take from 5 to 10 years to develop after total removal of the vitamin from the diet (for example, by adoption of a strict vegetarian diet). Some of the biliary vitamin is lost in the feces, and some is also excreted in the urine. The total excretion seems to be proportional to the total vitamin BI2 content of the body; as the result of low intake and tissue reserves, excretion is reduced. Consequently, a wide range of intakes can maintain adequate tissue levels ofthevitamin to support normal function.
