Vitamin Bseveral has the largest and most complex chemical structure of all the vitamins. For this reason cobalamin is the term used to refer to compounds having vitamin B12 activity. Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 used in the human body (1). The form of cobalamin used in most nutritional supplements and fortified foods, cyanocobalamin, is readily converted to 5-deoxyadenosylcobalamin and methylcobalamin in the body. In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase and L-methylmalonyl-coenzyme A mutase (2).
Cofactor for methionine synthase
Methylcobalamin needs into the purpose of the folate-created chemical, methionine synthase. It chemical becomes necessary into synthesis of one’s amino acid, methionine, out of homocysteine. Methionine consequently needs to the synthesis out-of S-adenosylmethionine, a great methyl group donor included in many biological methylation reactions, for instance the methylation from a great amount of web sites within DNA, RNA, and you will proteins (3). Aberrant methylation regarding DNA and you may healthy protein, that causes alterations in chromatin design and you can gene expression, was a familiar feature off disease tissue. Useless purpose of methionine synthase can result in an accumulation homocysteine, which has been of this improved risk of cardiovascular disease (Profile step 1).
Cofactor to have L-methylmalonyl-coenzyme A great mutase
5-Deoxyadenosylcobalamin is needed by enzyme you to catalyzes new transformation out-of L-methylmalonyl-coenzyme An inside succinyl-coenzyme A (succinyl-CoA), which in turn enters the fresh new citric acidic course (Profile dos). Succinyl-CoA takes on a crucial role regarding the production of time away from lipids and you can proteins and is also required for the formation of hemoglobin, the fresh oxygen-carrying pigment in yellow bloodstream muscle (3).
In healthy adults, vitamin B12 deficiency is uncommon, mainly because total body stores can exceed 2,500 ?g, daily turnover is slow, and dietary intake of only 2.4 ?g/day is sufficient to maintain adequate vitamin B12 status (see RDA) (4). In elderly individuals, vitamin B12 deficiency is more common mainly because of impaired intestinal absorption that can result in in B12 deficiency in this population.
Causes of nutritional B12 deficit
Intestinal malabsorption, rather than inadequate dietary intake, can explain most cases of vitamin B12 deficiency (5). Absorption of vitamin B12 from food requires normal function of the stomach, pancreas, and small intestine. Stomach acid and enzymes free vitamin B12 from food, allowing it to bind to R-protein (also known as transcobalamin-1 or haptocorrin), found in saliva and gastric fluids. In the alkaline environment of the small intestine, R-proteins are degraded by pancreatic enzymes, freeing vitamin B12 to bind to intrinsic factor (IF), a protein secreted by specialized cells in the stomach. Receptors on the surface of the ileum (final part of the small intestine) take up the IF-B12 complex only in the presence of calcium, which is supplied by the pancreas (5). Vitamin B12 can also be absorbed by passive diffusion, but this process is very inefficient-only about 1% absorption of the vitamin B12 dose is absorbed passively (2). The prevalent causes of vitamin B12 deficiency are (1) an autoimmune condition known as pernicious anemia, and (2) a disorder called food-bound vitamin B12 malabsorption. Both conditions have been associated with a chronic inflammatory disease of the stomach known as atrophic gastritis.
Atrophic gastritis is thought to affect 10%-30% of people over 60 years of age (6). The condition is frequently associated with the presence of autoantibodies directed toward stomach cells (see Pernicious anemia) and/or infection by the bacteria, Helicobacter pylori (H. pylori) (7). H. pylori infection induces chronic inflammation of the stomach, which may progress to peptic ulcer disease, atrophic gastritis, and/or gastric cancer in some individuals. Diminished gastric function in individuals with atrophic gastritis can result in bacterial overgrowth in the small intestine and cause food-bound vitamin B12 malabsorption. Vitamin B12 levels in serum, plasma, and gastric fluids are significantly decreased in individuals with H. pylori infection, and eradication of the bacteria has been shown to significantly improve vitamin B12 serum concentrations (8).