Methylcobalamin natural forms

The name vitamin B12 indicates a group of cobalt-containing corrinoids, also described as cobala-mins. Hydroxycobalamin (HOCbl), adenosylcobalamin (AdoCbl), and methylcobalamin (MeCbl) are the natural occurring forms. Instead, cyanocobalamin (Figure 19.20) is the commercially available form used for supplements and food fortification, thanks to its greater relative stability. Occasionally, sulfitocobalmin can occur in processed foods. Vitamin B,2 functions as a coenzyme and it is linked to human growth, cell development, and is involved in metabolism of certain amino acids. Vitamin B12 is present mainly in meat and diary foods, therefore a deficiency can occur in... 

In both bacteria and liver, the 5 -deoxyadenosyl coenzyme is the most abundant form of vitamin B12, while lesser amounts of methylcobalamin are present. Other naturally occurring analogs of the coenzymes include pseudo vitamin B12 which contains adenine in place of the dimethylbenzimidazole. 

During the course of biomethylation the methyl group is most likely transferred as a bridging intermediate rather than a free entity. Such an intermediate is assumed to form during an associative mechanism [4]. The methyl group may be electrophilic (cationic), radical or nucleophilic (anionic), depending on the specific donor moiety. A broad variety of methyl transfer reactions are therefore possible. Besides the two biological donors, methylcobalamin (see below) and S-adenosyl-methonine (1) nonenzymatic transmethylation is also possible in the natural environment, probably also very important for the formation and decomposition of metal methyl compounds [3b],... 

Mercury was the first element for which it was established that there is a natural route in the environment for conversion of the inorganic form to the methyl form (biomethylation). Minamata was caused by chemical formation of methylmercury from catalytic inorganic mercury within a vinyl chloride/acetic acid factory. However, discovery of methylmercury in river or estuarine sediments adjacent to chlor-alkali plants (where metallic mercury is used as a mobile cathode) suggested subsequent methylation of the mercury outside the factory. Such methylation was detected by Jensen and Jernelov in 1969. As discussed in Section 12.13.3.2, the responsible methylation agent was methylcobalamin (Table 4 and Figure 1). This reaction may be demonstrated in inorganic terms as attack of a methylcarbanion on Hg (Equation (8)). 

The Bi2a system was found to be easily reducible, first to Bi2r, and then to Bi2s (r stands for reduced and s for superreduced). Physical studies showed that Bi2r contains Co(II), and by comparison with model compounds, Bi2s was shown to contain Co(I), probably in a 4- or 5-coordinate form. The Bi2s state turns out to be one of the most powerful nucleophiles known, and it reacts rapidly with Mel, or the natural Me donor, N -methyl tetrahydro-folate, to give methylcobalamin. 

Cobalamins are essential enzymatic cofactors in human biochemistry. Coba-lamins chemical structure is based on the tetrapyrrole ring, while the chemical properties of the Co bond located in the centre of their moiety have been the focus of extensive research. Cyanocobalamin, the most known form of cobalamins, is rarely found in nature. Methylcobalamin and adenosylcobalamin are the two active forms of cobalamins in vivo in humans. Weakening of the Co C bond and its homolytic or heterolytic cleavage have been uncovered as an essential mechanism in the biochemical role of cobalamins as cofactors in humans. Recent studies using modem computational methods and application of quantum chemistry models have widened our knowledge of cobalamins biochemistry and are expected to contribute to our further understanding of cobalamin-dependent enzymes. 

There are five naturally occurring forms of cobalamins with methylcobalamin, adenosylcobalamin and hydroxycobalamin being the most frequently found forms. 

Cyanocobalamin (Formula 6.17) was isolated in 1948 from Lactobacillus lactis. Due to its stability and availability, it is the form in which the vitamin is used most often. In fact, cyanocobalamin is formed as an artifact in the processing of biological materials. Cobalamins occur naturally as adenosylcobalamin and methylcobalamin, which instead of the cyano group contain a 5 -deoxyadenosyl residue and a methyl group respectively. 

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