Vitamin Btwelve 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 to possess methionine synthase
Methylcobalamin needs to the reason for the brand new folate-depending chemical, methionine synthase. Which chemical is needed with the synthesis of your own amino acidic, methionine, out-of homocysteine. Methionine therefore is needed to the synthesis out-of S-adenosylmethionine, a beneficial methyl group donor found in of a lot biological methylation responses, like the methylation from a lot of websites contained in this DNA, RNA, and you may protein (3). Aberrant methylation of DNA and healthy protein, which causes alterations in chromatin build and you can gene phrase, is a familiar feature regarding disease structure. Inadequate intent behind methionine synthase can cause an accumulation homocysteine, that has been regarding the enhanced risk of heart problems (Contour 1).
Cofactor getting L-methylmalonyl-coenzyme An excellent mutase
5-Deoxyadenosylcobalamin needs of the enzyme one catalyzes the conversion out-of L-methylmalonyl-coenzyme A to succinyl-coenzyme An effective (succinyl-CoA), which in turn gets in the fresh new citric acidic years (Figure 2). Succinyl-CoA performs an important role about production of times of lipids and you may necessary protein and it is needed for the formation of hemoglobin, the brand new oxygen-carrying pigment in the reddish 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.
Reasons for 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 https://datingranking.net/escort-directory/kent/ 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).