Bi2—Cyanocobalamin

Bi2, cyanocobalamin racemization, decarboxylation, cleavage, synthesis, dehydration, and desulfhydration Methylation of homocysteine to mefliionine. 

The presence of the benzimidazole system in a natural product is most striking in the case of vitamin Bi2 (cyanocobalamin). It was isolated from liver extracts and from the fungus Streptomyces griseus. It is an antipemicious anaemia factor. Elucidation of its complex structure was achieved by X-ray analysis (Crawfoot-Hodgkin 1957). 5,6-Dimethylbenzimidazole is bonded via the atom N-I to D-ribose as an A -glycoside N-3 is linked to a cobalt ion which is situated in the centre of a corrin system (see p 489). 

Bi2, cyanocobalamin Microorganisms, liver Propionate metabolism Poor growth, anaemia, poor coat/feathering... 

Figure 47.1 Intracellular metabolism of vitamin Bi2- Cyanocobalamin is first converted into cob(II)alamin, which has no cyanogen group on the ligand occupying the upper axial position of the cobalamin structure. Cob(II)alamin is further reduced to cob(I)alamin, which can function as a coenzyme in the body. Removal of a cyanide molecule from cyanocobalamin is directly reduced by NADPH and flavoprotein in the presence of a cyanocobalamin trafficking chaperone. Cobalamin is reportedly converted into its inactive form, cob(H)alamin, under oxidative stress (Lemer-Ellis et al. 2006). NADPH nicotinamide adenine dinucleotide phosphate.

Bg (folic acid), Bi2 (cyanocobalamin) powders IS methotrexate 35"C Gradient elution with 0.1% aqueous formic acid and 0.1% formic acid in acetonitrile, at a flow rate of 0.2 ml/min. 

FIGURE 18.28 The structure of cyanocobalamin (top) and simplified structures showing several coenzyme forms of vitamin Bi2- The Co—C bond of 5 -deoxyadenosylcobalamin is predominantly covalent (note the short bond length of 0.205 nm) but with some ionic character. Note that the convention of writing the cobalt atom as Co" " attributes the electrons of the Co—C and Co—N bonds to carbon and nitrogen, respectively. 

The reduction of cyanocobalamin gives three possible oxidation states for the cobalt atom (Fig. 2). Electron spin resonance studies with Bi2-r reveals that this molecule is the only paramagnetic species giving a spectrum expected for a tetragonal low spin Co(II) complex. Controlled potential reduction of cyanocobalamin to Bi2-r proves that this reduction involves one electron, and further reduction of Bi2-r to B12-S requires a second single electron (16—19). At one time B12-S was considered to be a hydride of Co(III), but controlled potential coulometry experiments provided evidence against a stable hydride species (16). However, these experimental data do not exclude the possibility of a stable Co(III) hydride as the functional species in enzyme catalyzed oxidation reduction reactions. 

Microbiological assay should stress accuracy over precision. Standardization of an assay method should include comparisons with at least one other organism having a different nutritional pattern and specificity toward the compound being assayed. Such a comparison was made for cyanocobalamin (vitamin Bi2 ) content of human blood and serum, using four microorganisms differing in their cobamide requirements and metabolism (B9). 

Figure 15.3 Structural formula of deoxyadenosylcobalamin (coenzyme B, ). (a) A plan view of the corrin nucleus with substituents, (b) The position of the remaining two ligands of the cobalt atom. No attempt is made to show correct stereochemical relationships. Related compounds have different groups in place of the 5 -deoxyadenosyl group cyanocobalamin, (vitamin Bi2)-CN hydroxycobalamin, (vitamin Bi2)-0H methylcobalamin, (vitamin Bi2)-CH3.

Vitamin B12 consists of a porphyrin-like ring with a central cobalt atom attached to a nucleotide. Various organic groups may be covalently bound to the cobalt atom, forming different cobalamins. Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans. Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms. The ultimate source of vitamin Bi2 is from microbial synthesis the vitamin is not synthesized by animals or plants. The chief dietary source of vitamin Bi2 is microbially derived vitamin B12 in meat (especially liver), eggs, and dairy products. Vitamin Bi2 is sometimes called extrinsic factor to differentiate it from intrinsic factor, a protein normally secreted by the stomach that is required for gastrointestinal uptake of dietary vitamin B12. 

Vinyl polymerization, 332 Vitamin Bi2. See Cyanocobalamin Vitamin E. See Tocopherol Vitamin K, 43... 

Vitamin B12 for parenteral injection is available as cyanocobalamin or hydroxocobalamin. Hydroxocobalamin is preferred because it is more highly protein-bound and therefore remains longer in the circulation. Initial therapy should consist of 100-1000 Mg of vitamin Bi2 intramuscularly daily or every other day for 1-2 weeks to replenish body stores. Maintenance therapy consists of 100-1000 Mg intramuscularly once a month for life. If neurologic abnormalities are present, maintenance therapy injections should be given every 1-2 weeks for 6 months before... 

Acid is important in releasing vitamin B12 from food. A minor reduction in oral cyanocobalamin absorption occurs during proton pump inhibition, potentially leading to subnormal Bi2 levels with prolonged therapy. Acid also promotes absorption of food-bound minerals (iron, calcium, zinc) however, no mineral deficiencies have been reported with proton pump inhibitor therapy. 

In 1926 Minot and Murphy (4) announced that whole liver was effective in the treatment of pernicious anemia. The initial assay methods, which were clinical (5), coupled with what we now know are the exceptionally small amounts of Bi2 (even in a relatively rich source such as liver) required that two more decades pass before Folkers (6) and Smith (7) in 1948 simultaneously isolated crystalline vitamin Bi2 (1, R = CN). A further decade passed before it was realized that the so-called vitamin (cyanocobalamin) was an artifact of the isolation procedure and that the enzymatically active species is the vitamin Bi2 coenzyme (5 -deoxyadenosylcobalamin, 1, R = 5 -deoxyadenosyl). This initial observation arose during Barkers study on the conversion... 

Methylcobalamin (I, R = —CH3) and the vitamin Bi2 coenzyme (I, R = 5 -deoxyadenosyl) are the only known naturally occurring organometailic compounds. Both are derivatives of vitamin 8t2 (cyanocobalamin, I, R = —CN)and both can be synthesized from Bn but are best prepared from hydroxocobalamin. These and numerous other derivatives of Bn containing a cobalt-carbon bond are known, and provided the cobalt is bonded to a primary carbon atom the complexes are thermally very stable, but always photochemically labile as a result of homolytic cleavage of the cobalt-carbon bond. 

Bi2 (hydroxy/cyanocobalamin) Water 2.6 meg Cell mitosis detoxifies cyanide... 

---