Cobalamin cyanocobalamin

Cobalamine cyanocobalamin Pteroylglutamic add (PGA) folacin vitamin Be vitamin M... 

The total syntheses have yielded cobyric acid and thence cyanocobalamin. Routes to other cobalamins, eg, methylcobalamin and adenosylcobalamin, are known (76—79). One approach to such compounds involves the oxidative addition of the appropriate alkyl haUde (eg, CH I to give methylcobalamin) or tosylate (eg, 5 -A-tosyladenosine to yield adenosylcobalamine) to cobalt(I)alamine. 

The fibroblasts do not convert cyanocobalamin or hydroxocobalamin to methylcobalamin or adenosyl-cobalamin, resulting in diminished activity of both N5-methyltetrahydrofolate homocysteine methyltransferase and methylmalonyl-CoA mutase. Supplementation with hydroxocobalamin rectifies the aberrant biochemistry. The precise nature of the underlying defect remains obscure. Diagnosis should be suspected in a child with homocystinuria, methylmalonic aciduria, megaloblastic anemia, hypomethioninemia and normal blood levels of folate and vitamin B12. A definitive diagnosis requires demonstration of these abnormalities in fibroblasts. Prenatal diagnosis is possible. 

In biochemistry, metal hydrides such as NaBH4 have been widely used in synthesis. For example, NaBH4 has been used in the preparation of alkyl cobalamins from cyanocobalamin , and in the synthesis of the chiral [/3,y- 0 7 0, 0]ATPyS from the 5 -aldehyde of adenosine . Lithium triethylborohydride (also known as Su-... 

Vitamin B12 exists as hydroxocobalamin, adeno-sylcobalamin and cyanocobalamin. Cobalamins are found exclusively in food ingredients of animal origin like meat, liver and to a lesser degree in dairy products. Vitamin B12 is absorbed in the distal ileum under the influence of the glycoprotein intrinsic... 

Cyanocobalamin and the derivative hydroxo-cobalamin, given IM or deep subcutaneously, are indicated for treating vitamin B12 deficiency. Only in strict vegetarians oral preparations may be effective. Oral preparations with added intrinsic factor mostly are not reliably in patients with pernicious anemia. More than half the dose of cyanocobalamin injected is excreted in the urine within 48 hours and the therapeutic advantages of doses higher than 100 pg are questionable because of this rapid eiimination. As... 

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. 

Vitamin B12 consists of a porphyrin-like ring structure, with an atom of Co chelated at its centre, linked to a nucleotide base, ribose and phosphoric acid (6.34). A number of different groups can be attached to the free ligand site on the cobalt. Cyanocobalamin has -CN at this position and is the commercial and therapeutic form of the vitamin, although the principal dietary forms of B12 are 5 -deoxyadenosylcobalamin (with 5 -deoxyadeno-sine at the R position), methylcobalamin (-CH3) and hydroxocobalamin (-OH). Vitamin B12 acts as a co-factor for methionine synthetase and methylmalonyl CoA mutase. The former enzyme catalyses the transfer of the methyl group of 5-methyl-H4 folate to cobalamin and thence to homocysteine, forming methionine. Methylmalonyl CoA mutase catalyses the conversion of methylmalonyl CoA to succinyl CoA in the mitochondrion. 

Structure of vitamin B12 (cyanocobalamin) and its coenzyme forms (methylcobalamin and 5 -deoxyadenosyl-cobalamin). 

The metals copper, chromium and cobalt also appear to be essential for growth for some, if not all, microorganisms.1218 Cobalt is an essential requirement for cobalamin-utilizing bacteria, but apart from being an alternative substrate for an Mg2+ transport system, there appears to be no highly specific transport system for Co2+. E. coli has a high affinity uptake system for cyanocobalamin, even though it does not require Bl2. Cobalamin may thus serve as a source of cobalt. 

Figure 1 Schematic representation of the molecular structure, numbering of atoms, and designations of pyrrole rings of cobalamins. R = Me is methyl B12 R = Ado is adenosyl-cobalamin (coenzyme B12) X = CN is cyanocobalamin (vitamin B12). Five-membered rings are labeled A-D, and the amide side-chains are labeled a-g.

Interaction with Adenosylcobalamin. It has been considered generally that adenosylcobalamin or its analogs binds to the apoprotein of diol dehydrase or other adenosylcobalamin-dependent enzymes almost irreversibly (4). However, we found that the holo-enzyme of diol dehydrase was resolved completely into intact apoen-zyme and adenosylcobalamin when subjected to gel filtration on a Sephadex G-25 column in the absence of K+ (9, 10). Among the inactive complexes of diol dehydrase with irreversible cobalamin inhibitors, those with cyanocobalamin and methylcobalamin also were resolved upon gel filtration on Sephadex G-25 in the absence of both K+ and substrate, yielding the apoenzyme, which was reconstitutable into the active holoenzyme (II). The enzyme-hydroxocobalamin complex, however, was not resolvable under the same conditions. The enzyme-cobalamin complexes were not resolved at all by gel filtration in the presence of both K+ and substrate. When gel filtration of the holoenzyme was carried out in the presence of K+ only, the holoen-... 

Both Components F and S were required for irreversible cleavage of the C-Co bond of adenosylcobalamin by oxygen upon aerobic incubation with the coenzyme in the absence of substrate. This suggests that activation of the C-Co bond of the coenzyme is dependent on both components. Sephadex G-25 filtration experiments showed that neither adenosylcobalamin nor cyanocobalamin was bound by the individual components, F or S. Both of them were necessary for the cobalamin binding (8). 

The ligand attached to the cobalt atom determines the activity of vitamin B12 in human enzymatic reactions. The two active coenzyme forms are methyl-cobalamin and 5 -adenosylcobalamin, the primary form of vitamin B12 in tissues. Cyanocobalamin, the therapeutic form of vitamin B12 contained in vitamin supplements, is produced by the cleavage of the unstable fink... 

Oral vitamin Bj2 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin Bj2 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daUy. Parenteral therapy is more rapid acting than oral therapy and should be used if neurologic symptoms are present. A popular regimen is cyanocobalamin 1,000 meg daily for 1 week, then weekly for 1 month, and then monthly. When symptoms resolve, daily oral administration can be initiated. 

Figure 1 In the above structure, R = CN denotes cyanocobalamin (CN-Cbl), whilst R = OH is hydroxocobalamin (OH-Cbl) R = 5 -deoxyadenosyl is coenzyme B12 (adenosylcobalamin, AdoCbl) and R = Me is methylcobalamin (MeCbl). By definition all cobalamins contain 5,6-dimethylbenzimidazole, which is the so-called 6th ligand to cobalt in the above structure. Substances containing the corrin ligand, i.e. the planar 14 electron p-system embracing cobalt in the above structure, are also called corrinoids.

Cobalamins comprise a family of compounds which share a complex structure. Vitamin is known as cyanocobalamin because when originally isolated, an in-vitro artefact had placed a cyan group in the cobalt 3 position. Vitamin is an active cellular coenzyme essential for demethy-... 

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