Cobamamide, 腺苷钴胺

Coenzyme B12, also known as vitamin B12, is a coenzyme that participates in the metabolism of amino acids and fatty acids. It is required for the conversion of homocysteine to methionine, which is an important step in the synthesis of S-adenosylmethionine (SAM), a major methyl donor. Coenzymes are required for many different reactions in cells, but they are not consumed during these reactions. Instead, they are regenerated and reused. Coenzyme B12 is synthesized by bacteria and archaea but not by animals. The cobalamin form of this coenzyme is made from cobaltous chloride or cobaltous sulfate and cyanide. This coenzyme has been shown to bind to riboswitches in bacteria and to ATP-binding cassette transporters in humans. Coenzyme B12 can exist in two different forms: adenosylcobalamin and methylcobalamin.

Vitamin B12 cobalamin refers to a group of chemically-related cobalt containing molecules. The physiologically active forms of vitamin B12 include methylcobalamin and adenosylcobalamin, whereas hydroxocobalamin (vitamin B12a, OHCbl) and cyanocobalamin (CNCbl) are storage and delivery forms.

Coenzyme B12 (adenosylcobalamin; AdoCbl) is a biologically active form of vitamin B12. It belongs to the corrinoid group of compounds, which contain a corrin macrocycle, and is produced only by certain bacteria and archaea. It is a cofactor for various enzymes including mutases, eliminases, aminomutases, and a reductase. These enzymes catalyze reactions that generate free radicals through release of the adenosyl group, allowing usually unreactive molecules to become reactive. Only one of these enzymes, methylmalonyl CoA mutase, is found in mammals, therefore, the other enzymes must be taken in through the diet. Genetic mutations in enzymes that synthesize AdoCbl lead to AdoCbl deficiency and methylmalonic aciduria. Formulations containing AdoCbl are used to treat patients with this disorder.

Title: Cobamamide

CAS Registry Number: 13870-90-1

CAS Name: Co-(5'-deoxyadenosine-5') deriv of 3'-ester of cobinamide dihydrogen phosphate (ester) with 5,6-dimethyl-1-a-D-ribofuranosyl-1H-benzimidazole, inner salt

Additional Names: cobamamidum; coenzyme B12; DBC; adenosyl-B12; 5'-deoxyadenosyl-B12; 5'-deoxyadenosylcobalamine; dibencozide; dibenzcozamide; dimebenzcozamide; 5,6-dimethylbenzimidazolylcobamide coenzyme; 5,6-dimethylbenzimidazolylcobamide 5'-deoxyadenosine; vitamin B12 coenzyme

Trademarks: Actimide (Tobishi); Ademide (Toyo Jozo); Betarin (Beta); Calomide (Yamanouchi); Cobalion (Houd?; Cobaltamin S (Wakamoto); Cobanzyme (Bouchara); Cobazymase (Bouchara); Coenzile (A.T.I.); Dolonevran (Dausse); Enzicoba (Farmasa); Héraclène (Mauchant); Hi-Fresmin (Takeda); Hycobal (Eisai); Indusil (Diamant; Recordati); Ripresil (Erba); Sabalamin (Santen); Xobaline (Albert-Roussel)

Molecular Formula: C72H100CoN18O17P

Molecular Weight: 1579.58

Percent Composition: C 54.75%, H 6.38%, Co 3.73%, N 15.96%, O 17.22%, P 1.96%

Literature References: The coenzyme is the metabolically active form of vitamin B12: Barker et al., Proc. Natl. Acad. Sci. USA 44, 1093 (1958); Weissbach, Taylor, Vitam. Horm. 26, 395 (1968). Isoln from a culture of Propionibacterium shermanii: Barker et al., J. Biol. Chem. 235, 181, 480 (1960); Biochem. Prep. 10, 27 (1964). Prepn of aquocobalamin and 2',3'-O-isopropylidene-5'-O-p-tolylsulfonyladenosine: Hogenkamp, Pailes, ibid. 12, 124 (1968); from treatment of a cobalamin-thiol complex: Murakami et al., US 3461114 (1969 to Yamanouchi). The coenzyme differs from Vitamin B12 by the presence of a 5'-deoxyadenosyl group in the axial ligand occupied by the cyanide in the vitamin. Structure: Lenhert, Hodgkin, Nature 192, 937 (1961). The nucleoside is linked to the cobalt via the 5'-carbon atom of its deoxyribosyl moiety and the biological and chemical reactivity reside in this C to Co bond: Hogenkamp et al., J. Biol. Chem. 240, 3641 (1965) and Fed. Proc. 25, 1623 (1966). Review: Smith, Vitamin B12 (Methuen & Co., London, 3rd ed., 1965).

Properties: Yellow-orange six-faced crystals which become deep red upon exposure to air. Absorption max (H2O): 260, 375, 522 nm (A ´ 10-6 34.7, 10.9, 8.0 cm2/mole). Soly in water (24°): 16.4 mmol. Solns of pH <3.5 are yellow, >3.5, red. Sol in ethanol, phenol. Practically insol in acetone, ether, dichloroethylene, dioxane. pKa 3.5. Stability studies: Collado, Nieto, Ann. Pharm. Fr. 27, 427 (1969). Highly sensitive to light, to cyanide and moderately sensitive to acid. Solns are most stable at pH 6-7 stored in the dark. Heating of acid or alkaline solns produces slow inactivation.

pKa: pKa 3.5

Absorption maximum: Absorption max (H2O): 260, 375, 522 nm (A ´ 10-6 34.7, 10.9, 8.0 cm2/mole)

Therap-Cat: Vitamin (hematopoietic).

Therap-Cat-Vet: Vitamin (hematopoietic).

Keywords: Vitamin/Vitamin Source; Vitamin B12.