Consists of a corrin ring with a cobalt atom in its center attached to a nucleotide portion, a cobalamin compound.
Water soluble vitamin.
It is naturally present in some foods, added to others, and available as a dietary supplement and a prescription medication.
Essential for enzyme systems: adenosylcobalamin is a coenzyme in the conversion of methyl-malonyl-coenzyme A to succinyl coenzyme A, the synthesis of methionine from homocysteine and the synthesis of S-adenosyl methionine.
Vitamin B12 exists in several forms.
Vitamin B12 contains the mineral cobalt: compounds with vitamin B12 activity are collectively called cobalamins
Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 that are active in metabolism.
Vitamin B12 is required for proper red blood cell production, neurological function, and DNA synthesis.
A cofactor for only two enzymes: methionine synthase and L-methylmalonyl- coenzyme A mutase.
Methionine is required for the formation of S-adenosylmethionine, a universal methyl donor for almost 100 different substrates.
These substrates include: DNA, RNA, hormones, proteins, and lipids.
L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate, an essential biochemical reaction in fat and protein metabolism.
Succinyl-CoA is also required for hemoglobin synthesis.
The interaction between folate and B12 is responsible for megaloblastic anemias is seen in both vitamin deficiencies.A water soluble vitamin, necessary for neurologic functioning, hematopoiesis, and DNA synthesis.
Gastric acid is required for the release of vitamin B 12 from dietary proteins to facilitate absorption in the terminal ileum.
It is obtained exclusively from animal proteins, and absorbed in the ileum, facilitated by intrinsic factor.
B12 absorption decreases drastically when the capacity of intrinsic factor is exceeded.
Pernicious anemia is an autoimmune disease that affects the gastric mucosa, with gastric atrophy, and destruction of parietal cells, achlorhydria, and failure to produce intrinsic factor.
Pernicious anemia results in vitamin B12 malabsorption.
Untreated pernicious anemia causes vitamin B12 deficiency, leading to megaloblastic anemia and neurological disorders, even in the presence of adequate dietary intake of vitamin B12.
B12 is produced in nature only by certain bacteria and archaea.
B12 is not made by any animal, fungus, or plant.
B12 is synthesized by some gut bacteria in humans, but humans cannot absorb the B12 made in their guts, as it is made in the colon which is too far from the small intestine, where absorption of B12 occurs.
Animals store vitamin B12 in liver and muscle and some pass the vitamin into their eggs and milk; meat, liver, eggs and milk are therefore sources of B12.
It is measured with a competitive-binding immuno-enzymatic assay.
Intrinsic factor conjugate and paramagnetic particles coated with monoclonal immunoglobulin G anti-intrinsic factor are added to the sample.
The B12 binds to the intrinsic factor conjugate, blocking it from binding with the paramagnetic particles: A magnetic field holds the particle-bound to intrinsic factor in place while unbound materials are washed away and then a chemiluminescence substrate is added and the light is measured with a luminometer with the light production inversely proportional to the concentration of B12 in the sample.
Values below approximately 170-250 pg/mL (120-180 picomol/L) for adults indicate a vitamin B12 deficiency.
Serum vitamin B12 concentrations do not accurately reflect intracellular concentrations.
B12 sensitivity for deficiency detection is 95% at level is less than 200 pg/mL, but specificity is limited to 50%.
Serum B12 less than 400 pg/mL is considered suboptimal because 5-10% of patients with neurologic symptoms related to B12 insufficiency present with levels from 200 to 400 pg/mL.
At levels of 200 pg/mL, sensitivity is reduced and can be bolstered by serum methylmalonic acid.
During the Krebs cycle vitamin B 12 mediates the enzymatic conversion of methylmalonyl-coenzymeA to succinyl-coenzymeA- and methylmalonic levels greater than 0.75 mmol/L are suggestive of B12 deficiency.
In patients receiving PPIs for more than two years have a 65% increased risk for vitamin B 12 deficiency, compared with non-users.
Adenosyl-cobalamin is the tissue form of vitamin B12, and methylcobalamin circulates in the blood.
Absorbed in the terminal ileum as B12-intrinsic factor complex.
Daily requirement is 1-2 micrograms in adults.
Vitamin B 12 is found only an animal sourced foods: milk, eggs, and fish.
People who practice the strictest types of vegetarianism-veganism need to take supplements or consume vitamin B 12 fortified foods such as fortified cereals.
B12 levels can also be low in persons who consume a lacto-ovo vegetarian diet, which includes eggs and dairy products and low levels of our common in low and middle income countries where intake of animal source foods is limited.
Consequences of maternal vitamin B 12 depletion include poor fetal storage of vitamin B 12 and low concentrations in milk that can result in serious developmental delays in infants.
Older adults have increased prevalence of B12 deficiency as vitamin B12 absorption is impaired with reduced production of gastric acid which is needed to release the vitamin from foods.
The risk of vitamin B deficiencies increased in individuals with malabsorption conditions or who have undergo gastric bypass surgery.
Estimated 3.2% of adults older than 50 years have a low serum B12 levels.
A normal diet provides a large excess of vitamin B12.
The active absorption of vitamin B12 decreases from approximately 50% of the usual dietary intake to 4 to 6 µg per day to less than 1% at intakes above approximately 25 µg per day from supplements.
The passive absorption of one percent of intakes from high doses of vitamin B 12 of 500 to 1000 µg per day can improve status overtime in persons with the auto immune disease, pernicious anemia who lack gastric intrinsic factor.
Serum cobalamin levels lower in sickle cell disease patients than in control non sickle disease patients.
Following ingestion vitamin B12 initially binds to proteins carriers and then in the acidic environment of the stomach it dissociates from its protein carriers.
Intrinsic factor is manufactured by the parietal and zymogenic cells in the gastric fundus and body and binds to the free vitamin B 12 in the duodenum.
Binds to a glycoprotein, intrinsic factor, which is derived from the gastric mucosa.
Binding assay for vitamin B 12 can yield spuriously elevated results in patients with high levels of circular auto antibodies, including to intrinsic factor.
The intrinsic factor-vitamin B 12 complex is eventually absorbed by receptors in the terminal ileum.
Aside from active absorption via intrinsic factor, 1% of B12 is passively absorbed along the length of the small bowel.
Disturbance in any of the process above can lead to B12 deficiency.
Malabsorption of vitamin B12 can occur in patients who lose their ileal receptors, such as with inflammatory bowel disease, or have their terminal ileum resected.
Following reabsorption vitamin B12 dissociates again and binds to the transport protein transcobalamin II before entering the enterohepatic circulation.
Transcobalamin I is another transport protein and it is produced by gametocytes.
The liver is the major storage site with 2-3 mg, a thousand times excess of daily requirement.