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 having methionine synthase
Methylcobalamin is necessary towards the function of the newest folate-based enzyme, methionine synthase. That it chemical needs for the synthesis of your own amino acidic, methionine, off homocysteine. Methionine subsequently is needed to the synthesis off S-adenosylmethionine, an excellent methyl category donor included in of a lot physical methylation reactions, like the methylation of a good amount of internet within DNA, RNA, and you may proteins (3). Aberrant methylation of DNA and you will healthy protein, that triggers alterations in chromatin design and gene term, is actually a common element out of malignant tumors cells. Ineffective purpose of methionine synthase may cause an accumulation homocysteine, that has been of this enhanced risk of heart disease (Profile step 1).
Cofactor getting L-methylmalonyl-coenzyme A mutase
5-Deoxyadenosylcobalamin is necessary of the chemical you to definitely catalyzes the latest transformation of L-methylmalonyl-coenzyme A toward succinyl-coenzyme A (succinyl-CoA), which then goes into the citric acidic period (Contour 2). Succinyl-CoA plays an important role on creation of time away from lipids and you will necessary protein and is necessary for the formation of hemoglobin, the fresh new outdoors-carrying pigment into the red bloodstream tissue (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 because of impaired intestinal absorption that can result in in B12 deficiency in this population.
Causes of nutritional B12 insufficiency
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 Fresno backpage escort 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).