b12 blood increased level vitamin
Vitamin B12 is a water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins. It is normally involved in the metabolism of every cell of the body, especially affecting DNA synthesis and regulation, but also fatty acid synthesis and energy production.
Vitamin B12 is the name for a class of chemically-related compounds, all of which have vitamin activity. It is structurally the most complicated vitamin and it contains the biochemically rare element cobalt. Biosynthesis of the basic structure of the vitamin can only be accomplished by bacteria, but conversion between different forms of the vitamin can be accomplished in the human body. A common synthetic form of the vitamin, cyanocobalamin, does not occur in nature, but is used in many pharmaceuticals, supplements and as food additive, due to its stability and lower cost. In the body it is converted to the physiological forms, methylcobalamin and adenosylcobalamin, leaving behind the cyanide, albeit in minimal concentration. More recently, hydroxocobalamin, methylcobalamin and, adenosylcobalamin can also be found in more expensive pharmacological products and food supplements. The utility of these is presently debated.
Historically, vitamin B12 was discovered from its relationship to the disease pernicious anemia, which is an autoimmune disease that destroys parietal cells in the stomach that secrete intrinsic factor. Intrinsic factor is crucial for the normal absorption of B12, therefore, a lack of intrinsic factor, as seen in pernicious anemia, causes a vitamin B12 deficiency. Many other subtler kinds of vitamin B12 deficiency, and their biochemical effects, have since been elucidated.
Terminology
The name vitamin B12, known as vitamin B (commonly B or B12 for short) or also cyanocobalamin generally refers to all forms of the vitamin. Some medical practitioners have suggested that its use be split into two different categories, however.
- In a broad sense B12 refers to a group of cobalt-containing vitamer compounds known as cobalamins: these include cyanocobalamin (an artifact formed as a result of the use of cyanide in the purification procedures), hydroxocobalamin (another medicinal form), and finally, the two naturally occurring cofactor forms of B12: 5'-deoxyadenosylcobalamin (adenosylcobalamin—AdoB12), the cofactor of Methylmalonyl Coenzyme A mutase (MUT), and methylcobalamin (MeB12), the cofactor of 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR).
- The term B12 may be properly used to refer to cyanocobalamin, the principal B12 form used for foods and in nutritional supplements. This ordinarily creates no problem, except perhaps in rare cases of eye nerve damage, where the body is only marginally able to use this form due to high cyanide levels in the blood due to cigarette smoking, and thus requires cessation of smoking, or else B12 given in another form, for the optic symptoms to abate. However, tobacco amblyopia is a rare enough condition that debate continues about whether or not it represents a peculiar B12 deficiency which is resistant to treatment with cyanocobalamin.
Finally, so-called Pseudo-B12 refers to B12-like substances which are found in certain organisms, including Spirulina (a cyanobacterium) and some algae. These substances are active in tests of B12 activity by highly sensitive antibody-binding serum assay tests, which measure levels of B12 and B12-like compounds in blood. However, these substances do not have B12 biological activity for humans, a fact which may pose a danger to vegans and others on limited diets who do not ingest B12 producing bacteria, but who nevertheless may show normal "B12" levels in the standard immunoassay which has become the normal medical method for testing for B12 deficiency.
Structure
Vitamin B12 is a collection of cobalt and corrin ring molecules which are defined by their particular vitamin function in the body. All of the substrate cobalt-corrin molecules from which B12 is made must be synthesized by bacteria. However, after this synthesis is complete, the body has a limited power to convert any form of B12 to another, by means of enzymatically removing certain prosthetic chemical groups from the cobalt atom.
Cyanocobalamin is one such compound that is a vitamin in this B complex, because it can be metabolized in the body to an active co-enzyme form. However, the cyanocobalamin form of B12 does not occur in nature normally, but is a byproduct of the fact that other forms of B12 are avid binders of cyanide (-CN) which they pick up in the process of activated charcoal purification of the vitamin after it is made by bacteria in the commercial process. Since the cyanocobalamin form of B12 is deeply red colored, easy to crystallize, and is not sensitive to air-oxidation, it is typically used as a form of B12 for food additives and in many common multivitamins. However, this form is not perfectly synonymous with B12, inasmuch as a number of substances (vitamers) have B12 vitamin activity and can properly be labeled vitamin B12, and cyanocobalamin is but one of them. (Thus, all cyanocobalamin is vitamin B12, but not all vitamin B12 is cyanocobalamin).
B12 is the most chemically complex of all the vitamins. The structure of B12 is based on a corrin ring, which is similar to the porphyrin ring found in heme, chlorophyll, and cytochrome. The central metal ion is cobalt. Four of the six coordination sites are provided by the corrin ring, and a fifth by a dimethylbenzimidazole group. The sixth coordination site, the center of reactivity, is variable, being a cyano group (-CN), a hydroxyl group (-OH), a methyl group (-CH3) or a 5'-deoxyadenosyl group (here the C5' atom of the deoxyribose forms the covalent bond with Co), respectively, to yield the four B12 forms mentioned above. Historically, the covalent C-Co bond is one of first examples of carbon-metal bonds to be discovered in biology. The hydrogenases and, by necessity, enzymes associated with cobalt utilization, involve metal-carbon bonds.
Synthesis
Vitamin B12 cannot be made by plants or animals as only bacteria have the enzymes required for its synthesis. The total synthesis of B12 was reported by Robert Burns Woodward and Albert Eschenmoser, and remains one of the classic feats of organic synthesis.
Species from the following genera are known to synthesize B12: Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Micromonospora, Mycobacterium, Nocardia, Propionibacterium, Protaminobacter, Proteus, Pseudomonas, Rhizobium, Salmonella, Serratia, Streptomyces, Streptococcus and Xanthomonas. Industrial production of B12 is through fermentation of selected microorganisms. Streptomyces griseus, a bacterium once thought to be a yeast, was the commercial source of vitamin B12 for many years. The species Pseudomonas denitrificans and Propionibacterium shermanii are more commonly used today. These are frequently grown under special conditions to enhance yield, and at least one company, Rhône-Poulenc of France, at one point used genetically engineered versions of one or both of these species. It is not clear whether Sanofi-Aventis, the company which the pharmaceutical division of Rhône-Poulenc merged into, has continued the use of genetically modified organisms.
Functions
Vitamin B12 is normally involved in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production. However, many (though not all) of the effects of functions of B12 can be replaced by sufficient quantities of folic acid (another B vitamin), since B12 is used to regenerate folate in the body. Most "B12 deficient symptoms" are actually folate deficient symptoms, since they include all the effects of pernicious anemia and megaloblastosis, which are due to poor synthesis of DNA when the body does not have a proper supply of folic acid for the production of thymine. When sufficient folic acid is available, all known B12 related deficiency syndromes normalize, save those narrowly connected with the B12 dependent enzymes Methylmalonyl Coenzyme A mutase (MUT), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase; and the buildup of their respective substrates (methylmalonic acid, MMA) and homocysteine.
Coenzyme B12's reactive C-Co bond participates in two types of enzyme-catalyzed reactions.
- Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine.
- Methyl (-CH3) group transfers between two molecules.
In humans, only two corresponding coenzyme B12-dependent enzymes are known:
- Methylmalonyl Coenzyme A mutase (MUT) which uses the AdoB12 form and reaction type 1 to catalyze a carbon skeleton rearrangement (the X group is -COSCoA). MUT's reaction converts MMl-CoA to Su-CoA, an important step in the extraction of energy from proteins and fats (for more see MUT's reaction mechanism). This functionality is lost in vitamin B12 deficiency, and can be measured clin
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