Vitamin Ba dozen 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 have methionine synthase
Methylcobalamin is necessary for the aim of the folate-dependent enzyme, methionine synthase. So it chemical is needed towards the synthesis of the amino acidic, methionine, of homocysteine. Methionine consequently is necessary for the synthesis of S-adenosylmethionine, an effective methyl category donor utilized in of a lot biological methylation responses, for instance the methylation from a great amount of websites within this DNA, RNA, and you can healthy protein (3). Aberrant methylation away from DNA and you will proteins, that triggers changes in chromatin structure and you may gene phrase, are a familiar element from cancers cells. Ineffective function of methionine synthase can lead to a collection of homocysteine, which has been associated with increased chance of cardiovascular disease (Shape step one).
Cofactor to own L-methylmalonyl-coenzyme A mutase
5-Deoxyadenosylcobalamin will become necessary from the enzyme you to catalyzes the newest sales out of L-methylmalonyl-coenzyme A toward succinyl-coenzyme A good (succinyl-CoA), which in turn enters the newest citric acidic cycle (Profile dos). Succinyl-CoA takes on a crucial role regarding the production of opportunity off lipids and you will necessary protein and is needed for the forming of hemoglobin, the fresh new oxygen-carrying pigment during the red blood tissues (3).
Insufficiency
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 https://datingranking.net/escort-directory/buffalo/ because of impaired intestinal absorption that can result in in B12 deficiency in this population.
Factors behind vitamin B12 deficiency
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
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).