Role of Vitamin B12 in Human Metabolic Processes

Role of vitamin B12 in human metabolic processes

Although the nutritional literature still uses the term vitamin B12, a more specific name for vitamin B12 is cobalamin. Vitamin B12 is the largest of the B complex vitamins, with a molecular weight of over 1000. It consists of a corrin ring made up of four pyrroles with cobalt at the center of the ring. There are several vitamin B12–dependent enzymes in bacteria and algae, but no species of plants have the enzymes necessary for vitamin B12 synthesis. This fact has significant implications for the dietary sources and availability of vitamin B12. In mammalian cells there are only two vitamin B12–dependent enzymes. 

One of these enzymes, methionine synthase, uses the chemical form of the vitamin which has a methyl group attached to the cobalt and is called methylcobalamin. The other enzyme, methylmalonyl CoA mutase, uses vitamin B12 with a 5’-adeoxyadenosyl moiety attached to the cobalt and is called 5’-deoxyaldenosylcobalamin, or coenzyme B12. In nature there are two other forms of vitamin B12: hydroxycobalamin and aquacobalamin, where hydroxyl and water groups, respectively, are attached to the cobalt. The synthetic form of vitamin B12 found in supplements and fortified foods is cyanocobalamin, which has cyanide attached to the cobalt. These three forms of B12 are enzymatically activated to the methyl- or deoxyadenosylcobalamins in all mammalian cells.

Dietary sources and availability

Most microorganisms, including bacteria and algae, synthesise vitamin B12, and they constitute the only source of the vitamin. The vitamin B12 synthesised in microorganisms enters the human food chain through incorporation into food of animal origin. In many animals gastrointestinal fermentation supports the growth of these vitamin B12–synthesising microorganisms, and subsequently the vitamin is absorbed and incorporated into the animal tissues. This is particularly true for the liver, where vitamin B12 is stored in large concentrations. Products from these herbivorous animals, such as milk, meat, and eggs, constitute important dietary sources of the vitamin unless the animal is subsisting in one of the many regions known to be geochemically deficient in cobalt. Milk from cows and humans contains binders with very high affinity for vitamin B12, whether they hinder or promote intestinal absorption is not entirely clear. Omnivores and carnivores, including humans, derive dietary vitamin B12 from animal tissues or products (i.e., milk, butter, cheese, eggs, meat, poultry, etc.). It appears that no significant amount of the required vitamin B12 by humans is derived from microflora, although vegetable fermentation preparations have also been reported as being possible sources of vitamin B12.

Absorption

The absorption of vitamin B12 in humans is complex. Vitamin B12 in food is bound to proteins and is released from the proteins by the action of a high concentration of hydrochloric acid present in the stomach. This process results in the free form of the vitamin, which is immediately bound to a mixture of glycoproteins secreted by the stomach and salivary glands. These glycoproteins, called R-binders (or haptocorrins), protect vitamin B12 from chemical denaturation in the stomach. The stomach’s parietal cells, which secrete hydrochloric acid, also secrete a glycoprotein called intrinsic factor. Intrinsic factor binds vitamin B12 and ultimately enables its active absorption. Although the formation of the vitamin B12 – intrinsic factor complex was initially thought to happen in the stomach, it is now clear that this is not the case. At an acidic pH the affinity of the intrinsic factor for vitamin B12 is low whereas its affinity for the R-binders is high. When the contents of the stomach enter the duodenum, the R-binders become partly digested by the pancreatic proteases, which causes them to release their vitamin B12. Because the pH in the duodenum is more neutral than that in the stomach, the intrinsic factor has a high binding affinity to vitamin B12, and it quickly binds the vitamin as it is released from the R-binders. The vitamin B12–intrinsic factor complex then proceeds to the lower end of the small intestine, where it is absorbed by phagocytosis by specific ileal receptors.

References:

Weir, D.G. & Scott, J.M. 1999. Cobalamins Physiology, Dietary Sources and Requirements. In: Sadler M.J., Strain J.J., Caballero B., eds. Encyclopedia of Human Nutrition, 1: 394-401.

Weir, D.G. & Scott, J.M. 1999. In: Modern Nutrition in Health and Disease. Editors Shils M.E., Olson J.A., Shike M., & Ross A.C. Baltimore, USA. Willams and Wilkins.

Scott, J.M. & Weir, D.G. 1994. Folate/vitamin B12 interrelationships. Essays in Biochemistry, p.63-72.

Chanarin, I. 1979. The Megaloblastic Anaemia 2nd Edition. London. Blackwell Scientific Oxford.

Smith, R. & Cobalt, M. 1987. In: Trace Elements in Human and Animal Nutrition, 5th Edition. Ch. 5(editor: Mertz W.) p. 143-184. San Diego, Academic Press.

Van den Berg, H., Dagnelie H. & van Staveren, W.A. 1998. Vitamin B12 and seaweed. Lancet, 1: 242-243.