Adenosylcobalamin 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... 

The Bj2 vitamers consist of a group of organometallic compounds that have a common cor-rinoid structure and vary in the substituent bound to the central cobalt atom (Fig. 7) (167,168). The principal naturally occurring Bl2 vitamers are hydroxocobalamin (HOCbl), methylcobal-amin (MeCbl), and adenosylcobalamin (AdoCbl). Cyanocobalamin (CNCbl) is the form commonly used for clinical, pharmaceutical, and food fortification purposes, due to its greater relative stability. 

S-Methylmalonyl-CoA mutase (EC 5.4.99.2) is a deoxyadenoxyladen-osylcobalamin-dependent enzyme of mitochondria required to catalyze the conversion of methylmalonyl-CoA to succinyl-CoA. A decrease in the activity of methylmalonyl-CoA mutase leads to the urinary excretion of large amounts of methylmalonic acid (C22). The biochemical lesion may be at the mutase level due to an abnormality of apoenzyme protein or an inability to elaborate the required coenzyme form of vitamin B12> i.e., adenosyl-cobalamin. In rare cases the abnormality may be due to an inability to convert the d form of methylmalonyl-CoA mutase to the l form as a result of a defective racemase (EC 5.1.99.1) (Kll). In patients, the nature of the abnormality can be determined by tissue culture studies (D13) and by clinical trial, since patients with a defect in adenosylcobalamin production will show clinical improvement when treated with very large doses of vitamin B12 (Mil). 

The cobalt-containing vitamin or cyanocobalamin and its biologically active form, coenzyme B12 or adenosylcobalamin (Figure 9.1), represent some of the most complex organometallic compounds found in nature. 

A separate pathway has evolved to build a-ribazole 84, unusual both in its base, 5,6-dimethylbenzimidazole, and in the a-linkage to ribose. Either a-ribazole 84 or its 5 -phosphate 85 is able to accept the adenosylcobinamide phosphate residue from adenosyl-GDP-cobinamide 83, a transfer catalysed by CobV, to form adenosylcobalamin (coenzyme B12, 4) or its 5 -phosphate, respectively. Dephosphorylation of the 5 -phosphate then leads to 4. Thus the end product from nature s marathon, coenzyme 4, has been reached, a structure of marvellous architecture and amazing biological activity. 

Before the crystal structure of adenosylcobalamin became known, coenzyme Bj2 had been described as an adenine derivative of vitamin Bi2- Taking into consideration the cobaltic nature of coenzyme B12, the mechanism in Figure 2(a) for the reaction of MCM was put forward in 1960. This was a proton-coupled electron transfer and free radical mechanism, in which the Co of coenzyme Bj2 was postulated to potentiate the removal of an electron and proton from the substrate to form a carbon-centered substrate radical and Co. The substrate radical would undergo rearrangement to the product-related radical, which would then accept an... 

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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