Vitamin B12 Methylcobalamin

What is cobalamin ?

Cobalamines, also known as vitamin B12 or extrinsic factor, form a group of macrocyclic organometallic compounds having a mono-, di- or tri-positively charged cobalt ion. They are the only known naturally-occurring cobalt-containing compounds in nature. Cobalamin was discovered in 1926, and was isolated from the liver. Cobalamines can take a number of forms, including cyano-, methyl-, deoxyadenosyl- and hydroxycobalamin. All forms of cobalamin can be converted into the methyl or 5 deoxyadenosyl forms which are necessary as cofactors a number of important enzymes.

Structure

Cobalamines form a group of macrocyclic organometallic compounds with a single, dual-or triple positively charged cobalt ion.

The structure of cobalamines is based on two characteristic components:

• a corrin ring, which is similar to the porphyrin ring in heme, chlorophyll and cytochrome. The central metal ion is cobalt herein. The cobalt is very closely linked to the corrin and can really only by destroying the ring structure are detached therefrom.
• a ribonucleotide (5,6 dimethylbenzimidazole ribonucleotide)

Four are occupied by the six coordination positions of the central cobalt atom by the corrin ring and a fifth by a dimethylbenzimidazolgroep. The last of the six coordination positions of the central cobalt atom is much less strongly bound to the cobalt (with a residue R of group indicated), and through there to bind different ligands may result in different forms of vitamin B12.

• a cyanide. This form of vitamin B12 is known as cyanocobalamin. Cyanocobalamin is not normally found in nature, but is used in many pharmaceuticals and dietary supplements because of its stability and low cost. In the body, it can be converted into the metabolically active forms of vitamin B12: methylcobalamin and adenosylcobalamin, in which cyanide is released (albeit in minute amounts).
• a hydroxyl group: hydroxocobalamin This form is often used for intra-muscular injections.
• a methyl group: methylcobalamin
• 5'deoxyadenosine (adenine at ribose): also known as adenosylcobalamin, 5.6-dimethylbenzimidazolylcobamide-5'-deoxyadenosine, dibencoside, cobamide or coenzyme B12.

The cells come cobalamines in mitochondria mainly 5'-desoxyadenosylcobalamine (coenzyme B12) for, in the cytosol by contrast predominantly as methylcobalamine. In nutritional vitamin B12 is usually bound to a protein in the methyl or 5'deoxyadenosylvorm. Also, the conversion in the body of each form of B-12 is done via the methylcobalamin or 5'-deoxyadenosylcobalamin. The latter two forms are actively involved in the endogenous metabolism. Methylcobalamin, and 5'-deoxyadenosylcobalamin are considered to be derivatives of the natural vitamin B12.

The covalent C-Co compound in, for example, methylcobalamin is one of the first examples of carbon-metal compounds that have been discovered in nature. All four of the connections between cobalt and the (nitrogen groups of the) corrinemoleculen have to be made by bacteria. When these connections are completed, the body has only a modest capacity to absorb vitamin B12 in one of the other forms of B12 to be converted.

Features

Cobalamines are cofactors of various enzymes and sailed out their biological role:

• Methylcobalamin is a cofactor in the enzyme methionine synthase. This enzyme contributes to the methyl group of folic acid (5-methyltetrahydrofolate), which in turn over on homocysteine ​​methionine is created, an amino acid that is essential for the DNA-synthesis. A deficiency of cobalamin, therefore, leads to a problem with rapidly dividing cells, that need to create a lot of DNA. The most obvious is that for red blood cells, but also the lining of the gut, the vagina and tongue can be created less well. In addition, methionine synthase is essential for the synthesis of purines and pyrimidines. Thus vitamin B12 is essential for the synthesis of DNA and cellular energy production.
• Another function of cobalamin is to stimulate the formation of myelin. This protein envelops the nerve so that the suckers of the nerve impulse conduction is accelerated.
• Methylcobalamin is a cofactor in the enzyme L-methyl-malonyl-CoA mutase. It is a defect in this reaction and the subsequent accumulation of methylmalonyl CoA, which is considered responsible for the neurological effects of vitamin B12 deficiency.
• Methylcorrinoïdes, such as methylcobalamin, are co-factors of enzymes in the carbon dioxide binding by anaerobic acetate-forming bacteria and methanogenic archaea.
• Cobalamines are cofactors of enzymes in anaerobic sulfate-reducing bacteria which are able to convert aliphatic and aromatic chlorinated hydrocarbons.