Cobalamins represent chemical compounds that belong to the vitamin B12 group. They are found in all organisms. Their synthesis occurs only by bacteria.
What are cobalamins?
Cobalamins are a group of chemical compounds with the same basic structure that belong to the vitamin B12 complex. They are a complex compound with cobalt as the central atom. They are considered the only cobalt-containing natural products known to date. The cobalt atom is surrounded by a total of six ligands. Four ligands each represent a nitrogen atom of a planar corrin ring system. The fifth nitrogen atom belongs to a 5,6-dimethyl-benzimidazole ring, which is attached to the corrin ring in a nucleotide-like manner. A sixth ligand is very easily attached and exchangeable. Only this exchangeable ligand characterizes the specific compound present. The actual vitamin B12 contains a cyano radical as the sixth ligand and is accordingly called cyanocobalamin. Other important cobalamins include aquacobalamin (vitamin B12a), hydroxycobalamin (vitamin B12b), nitrritocobalamin (vitamin B12c), methylcobalamin (methyl-B12, MeCbl) and, as an extremely significant coenzyme, adenosylcobalamin (coenzyme B12). All of these compounds also represent storage forms of vitamin B12. In medicine, cyanocobalmin is the only vitamin B12 that can be applied. It is immediately converted into coenzyme B12 in the body. All storage forms of the active ingredient are absorbed through food. For humans, vitamin B12 synthesized by bacteria in the colon is not usable because cobalamin absorption occurs in the small intestine.
Function, effects, and roles
Vitamin B12 performs important functions in blood formation, cell division, and the nervous system. In the organism, it participates in only two enzymatic reactions, but they have a central biological significance. The enzyme N5-methyl-tetrahydrofolate-homocysteine-S-methyltransferase (methionine synthase) functions as a methyl group donor with the help of coenzyme B12. Methionine synthase reactivates the methyl group transmitter S-adenosylmethionine (SAM) on the one hand and remethylates homocysteine to methionine on the other. In the case of vitamin B12 deficiency or failure, homocysteine accumulates in the blood. Increased homocysteine concentrations are a risk factor for arteriosclerosis. Furthermore, the enzyme N5-methyl-THF also accumulates, causing a secondary deficiency of THF (tetrahydrofolic acid). THF supports the assembly of the purine bases adenine and guanine as well as the pyrimidine base thymine. The nitrogen bases are involved in the assembly of the nucleic acids DNA and RNA. Therefore, when THF is lacking, nucleic acid synthesis is disrupted. The second function of vitamin B12 is to support the enzyme methylmalonyl-CoA mutase. Methylmalonyl-CoA mutase degrades odd-numbered fatty acids to form propionyl-CoAs. Propionyl-CoAs is then introduced into the citric acid cycle. A metabolite of this process is methylmalonyl-CoA. When vitamin B12 is lacking, methylmalonyl-CoA accumulates, which can then lead to neurologic symptoms.
Formation, occurrence, properties, and optimal levels
Cobalamins cannot be produced in plant, animal, or human metabolism. Only some bacteria are able to synthesize this active ingredient. These include human intestinal bacteria. Since cobalamin synthesis in humans takes place in the large intestine, but the absorption of vitamin B12 takes place in the small intestine with the help of the intrinsic factor, the cobalamin formed in the intestine cannot be used. Humans are dependent on the supply from food. At the same time, a biochemical process exists that allows vitamin B12 to be transported back into the small intestine again and again by means of bile acids, where it is reabsorbed. As a result, a once-filled store in the liver lasts for several years, even if there is no supply of vitamin B12. The liver can store 2000 to 5000 micrograms of cobalamin. The minimum daily requirement for adults is about 3 micrograms. In children, the requirement is lower and increases over time. Pregnant and lactating women have a higher requirement, which is 3.5 to 4 micrograms per day. After 450 to 750 days, half of the available cobalamin is used up. Important sources of cobalamin are liver and offal of various farm animals, herring, beef, cheese, chicken egg or tuna. Vitamin B12 is almost absent from plant foods. In vegetarian lifestyles, additional supplementation must be taken.
Diseases and disorders
Because of the high importance of the biochemical reactions supported by cobalamins, a deficiency of vitamin B12 leads to severe health problems. Deficiency may result from a purely vegetarian diet on the one hand and may be due to the failure of intrinsic factor on the other. The intrinsic factor is a glycoprotein that binds cobalamin in the small intestine, thus making it available for reuse. This protein is produced in the gastric vestibular cells. In gastric diseases with failure of the ventricular cells, intrinsic factor can no longer be produced. A renewed use of the existing cobalamin is no longer possible. The lack of vitamin B12 inhibits the methylation of homocysteine to methionine. The homocysteine level in the blood rises and the risk of arteriosclerosis increases. At the same time, N5-methyl-tetrahydrofolate ((N5-methyl-THF) accumulates. A deficiency of THF occurs. As a result, nucleic acid synthesis no longer functions properly. Processes with a high nucleic acid requirement, such as hematopoiesis, are inhibited. The number of blood cells decreases, with the remaining erythrocytes increasing in size due to replenishment with hemoglobin. As a result, a so-called pernicious (malignant) anemia develops, which is not caused by iron deficiency. It can be treated by administration of folic acid. However, the cobalamin deficiency persists and still causes neurological symptoms such as funicular myelosis or polyneuropathies via the disruption of methylmalonyl-CoA mutase by accumulation of methylmalonic acid in the plasma.
