Cyanocobalamin

Cyanocobalamin
Identifiers
CAS number	68-19-9 Y
PubChem	16212801
EC number	200-680-0
DrugBank	DB00115
ChEMBL	CHEMBL1200658 N
Properties
Molecular formula	C63H88CoN14O14P
Molar mass	1355.38 g/mol
Appearance	Dark red solid
Melting point	> 300 °C
Boiling point	> 300 °C
Solubility in water	Soluble
Hazards
MSDS	External MSDS from Fisher Scientific
EU classification	Not available
S-phrases	S24/25
NFPA 704	1 1
Flash point	N/A
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Cyanocobalamin is an especially common vitamer of the vitamin B₁₂ family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable. It is the easiest to crystallize and, therefore, easiest to purify after it is produced by bacterial fermentation, or synthesized in vitro.

Vitamin B₁₂ is the name for a whole class of chemicals with vitamin B₁₂ activity, and cyanocobalamin is only one of these. Cyanocobalamin usually does not even occur in nature, and is not one of the forms of the vitamin that are directly used in the human body (or that of any other animal). However, animals and humans can convert cyanocobalamin to active (cofactor) forms of the vitamin, such as methylcobalamin.^[1] This process happens by equilibration, as cyanocobalamin slowly loses its cyanide in surroundings that contain no cyanide.^{[citation needed]}

Chemical properties

This compound is found as dark red crystals or an amorphous or crystalline red powder. Cyanocobalamin is very hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). It is stable to autoclaving for short periods at 121 °C. The vitamin B₁₂ coenzymes are very unstable in light.

Production

Since vitamin B₁₂ has a 40-step very difficult totally synthetic route (the longest of any vitamin), this compound is always commercially prepared instead by bacterial fermentation. Fermentation by a variety of microorganisms gives a mixture of methyl-, hydroxo-, and adenosylcobalamin. These compounds are extracted, then converted to cyanocobalamin by addition of potassium cyanide in the presence of sodium nitrite and heat. Cyanocobalamin is not produced directly by any species of bacterium, but compounds with vitamin B₁₂ activity can be made by many bacterial species. Since a number of species of Propionibacterium produce no exotoxins or endotoxins and are generally regarded as safe (have been granted GRAS status) by the Food and Drug Adminstration of the United States, they are presently the preferred bacterial fermentation organisms for vitamin B₁₂ production.^[2]

Historically, a form of vitamin B₁₂ called hydroxocobalamin is often produced by bacteria, and was then changed to cyanocobalamin in the process of being purified in activated charcoal columns after being separated from the bacterial cultures. This change was not immediately realized when vitamin B₁₂ was first being extracted for characterization. Cyanide is naturally present in activated charcoal, and hydroxocobalamin, which has great affinity for cyanide, picks it up, and is changed to cyanocobalamin. Cyanocobalamin is the form in most pharmaceutical preparations because adding cyanide stabilizes the molecule.^[1]

France accounts for 80 % of world production, and more than 10 tonnes/year of this compound is sold; 55 % of sales is destined for animal feed, while the remaining 45 % is for human consumption.^[3]

Pharmaceutical use

Cyanocobalamin is usually prescribed for the following reasons: after surgical removal of part or all of the stomach or intestine to ensure there are adequate levels of vitamin B₁₂ in the bloodstream; to treat pernicious anemia; vitamin B₁₂ deficiency due to low intake from food; thyrotoxicosis; hemorrhage; malignancy; liver or kidney disease. Cyanocobalamin injections are often prescribed to gastric bypass patients having had part of their small intestine bypassed, making it difficult for B₁₂ to be absorbed via food or vitamins. Cyanocobamide is also used to perform the Schilling test to check a person's ability to absorb vitamin B₁₂.^[4]

End Product of Cyanide Poisoning Treatment

In cases of Cyanide poisoning the patient is given hydroxocobalamin, which is a precursor to cyanocobalamin. The hydroxocobalamin binds with the cyanide ion and forms cyanocobalamin which can then be secreted by the kidneys. This has been used for many years in France and was approved by the FDA in Dec 2006, marked under the name Cynokit.^[5]

Possible side effects

The oral use of cyanocobalamin may lead to several allergic reactions such as hives; difficult breathing; swelling of the face, lips, tongue, or throat. Less-serious side effects may include headache, nausea, stomach upset, diarrhea, joint pain, itching, or rash.^[6]

In the treatment of some forms of anemia (e.g., megaloblastic anemia), the use of cyanocobalamin can lead to severe hypokalemia, sometimes fatal, due to intracellular potassium shift upon anemia resolution (but this same effect should be observed with any B12 vitamer, not just cyanocobalamin). When treated with vitamin B₁₂, patients with Leber's disease may suffer rapid optic atrophy.^{[citation needed]}

Cyanide is present in almost every type of smoke produced by burning organic materials, including tobacco and cannabis; therefore, there is some concern^{[by whom?]} that vitamin B₁₂-deficient smokers should not be given cyanocobalamin, as it will have more difficulty being broken down.^{[citation needed]} In such cases, other forms of vitamin B₁₂ for injection (such as hydroxocobalamin itself) are commonly available as pharmaceuticals, and are actually the most commonly used injectable forms of vitamin B₁₂ in many countries. Injectable cyanocobalamin remains the most commonly injectable vitamin B₁₂ in the United States.

See also

• Cobamamide
• Hydroxocobalamin
• Methylcobalamin
• Vitamin B12

References

1. ^ ^{a b} Victor Herbert (1988). "Vitamin B-12: plant sources, requirements, and assay". American Journal of Clinical Nutrition 48 (3 Suppl): 852–8. PMID 3046314. http://www.ajcn.org/cgi/reprint/48/3/852.pdf. 
2. ^ Riaz, Muhammad; Fouzia Iqbal and Muhammad Akram (2007). "Microbial production of vitamin B12 by methanol utilizing strain of Pseudomonas specie". Pak J. Biochem. Mol. Biol. 1 40: 5–10. http://pu-pk.academia.edu/MuhammadAkram/Papers/83315/Microbial_production_of_vitamin_B12_by_methanol_utilizing_strain_of. 
3. ^ Bruno Kaesler (2005), "Vitamins: 9. Vitamin B12 (Cyanocobalamins)", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, doi:10.1002/14356007.a27_443 
4. ^ http://www.umm.edu/altmed/drugs/cyanocobalamin-033700.htm
5. ^ Bledsoe, Bryan (2009). Paramedic Care: Principles & Practice, Medical Emergencies. Upper Saddle River, New Jersey: Pearson Education, Inc. pp. 471. ISBN 978-0-13-513702-4. 
6. ^ cyanocobalamin (oral). Cerner Multum, Inc. (Healthwise). 2009-04-21. http://health.msn.com/medications/articlepage.aspx?cp-documentid=100106512