Cobalamin Coenzymes and Vitamin B12

Wolfgang Buckel, Philipps‐Universität, Marburg, Germany

Published online: September 2007

DOI: 10.1002/9780470015902.a0000666.pub2

Cobalamins are derivatives of vitamin B12 that serve as cofactors in various enzymatic reactions involving either radicals or supernucleophilic intermediates.

Keywords: cobalt–carbon bond; 5¢-desoxyadenosyl radical; carbon skeleton rearrangement; amino mutase; elimination; methyl transfer

Figure 1. Structure of cobalamins.
Figure 2. General reaction mechanism postulated for AdoCbl-dependent mutases; R• = 5¢-deoxyadenosyl radical or Ado-CH2•, X = migrating group. The mechanism of step III is only solved in glutamate mutase. In case of the eliminases an additional step V is necessary to eliminate water or ammonia. In ribonucleotide reductase R• generates a thiyl radical, which abstracts the 3¢-hydrogen atom (step II). From the resulting substrate radical water is eliminated followed by a two-electron reduction and final redonation of the initially abstracted hydrogen atom, whereby R• is regenerated.
Figure 3. Postulated reaction mechanism for methionine synthase.
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 References
    book Banerjee R (1999) Chemistry and Biochemistry of B12. New York: John Wiley & Sons Inc.
    Banerjee R (2006) B12 trafficking in mammals: A for coenzyme escort service. American Chemical Society, Chemistry and Biology 1: 149–159.
    Barker HA, Weissbach H and Smyth RD (1958) A coenzyme containing pseudovitamin B12. Proceedings of the National Academy of Sciences of the USA 44: 1093–1097.
    Bothe H, Darley DJ, Albracht SP et al. (1998) Identification of the 4-glutamyl radical as an intermediate in the carbon skeleton rearrangement catalyzed by coenzyme B12-dependent glutamate mutase from Clostridium cochlearium. Biochemistry 37: 4105–4113.
    Brock M, Maerker C, Schütz A, Völker U and Buckel W (2002) Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase. European Journal of Biochemistry 269: 6184–6194.
    Brown KL (2005) Chemistry and enzymology of vitamin B12. Chemical Reviews 105: 2075–2149.
    Buckel W and Golding BT (1996) Glutamate and 2-methyleneglutarate mutase: from microbial curiosities to paradigms for coenzyme B12-dependent enzymes. Chemical Society Reviews 25: 329–337.
    Buckel W, Kratky C and Golding BT (2005) Stabilisation of methylene radicals by cob(ii)alamin in coenzyme B12 dependent mutases. Chemistry A European Journal 12: 352–362.
    Chih HW and Marsh ENG (2000) Mechanism of glutamate mutase: identification and kinetic competence of acrylate and glycyl radical as intermediates in the rearrangement of glutamate to methylaspartate. Journal of the American Chemical Society 122: 10732–10733.
    Drennan CL, Matthews RG and Ludwig ML (1994) Cobalamin-dependent methionine synthase: the structure of a methylcobalamin-binding fragment and implications for other B12-dependent enzymes. Current Opinion in Structural Biology 4: 919–929.
    Hagemeier CH, Krer M, Thauer RK, Warkentin E and Ermler U (2006) Insight into the mechanism of biological methanol activation based on the crystal structure of the methanol-cobalamin methyltransferase complex. Proceedings of the National Academy of Sciences of the USA 103: 18917–18922.
    Hay B and Finke R (1987) Thermolysis of the Co–C bond in adenosylcorrins. 3. Quantification of the axial base effect in adenosycobalamin by the synthesis and thermolysis of axial base-free adenosylcobinamides. Insights into the energetics of enzyme-assisted cobalt–carbon bond homolysis. Journal of the American Chemical Society 109: 8012–8018.
    Korotkova N and Lidstrom ME (2004) MeaB is a component of the methylmalonyl-CoA mutase complex required for protection of the enzyme from inactivation. Journal of Biological Chemistry 279: 13652–13658.
    Kräutler B, Fieber W, Ostermann S et al. (2003) The cofactor of tetrachloroethene reductive dehalogenase of Dehalospirillum multivorans is norpseudo-B12, a new type of a natural corrinoid. Helvetica Chimica Acta 86: 3698–3716.
    Lenhert PG and Hodgkin DC (1961) Structure of the 5,6-dimethyl-benzimidazolylcobamide coenzyme. Nature (London) 192: 937–938.
    Licht S, Gerfen GJ and Stubbe JA (1996) Thiyl radicals in ribonucleotide reductases. Science 271: 477–481.
    Mancia F, Keep NH, Nakagawa A et al. (1996) How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 Å resolution. Structure 4: 339–350.
    Masuda J, Shibata N, Morimoto Y, Toraya T and Yasuoka N (2000) How a protein generates a catalytic radical from coenzyme B12: X-ray structure of a diol-dehydratase-adeninylpentylcobalamin complex. Structure 8: 775–788.
    Matthews RG (2001) Cobalamin-dependent methyltransferases. Accounts of Chemical Reserach 34: 681–689.
    Pejchal R and Ludwig ML (2005) Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication. PLoS Biology 3: e31.
    Reitzer R, Gruber K, Jogl G et al. (1999) Glutamate mutase from Clostridium cochlearium: the structure of a coenzyme B12-dependent enzyme provides new mechanistic insights. Structure 7: 891–902.
    Shibata N, Mori K, Hieda N et al. (2005) Release of a damaged cofactor from a coenzyme B12-dependent enzyme: X-ray structures of diol dehydratase-reactivating factor. Structure 13: 1745–1754.
    Svetlitchnaia T, Svetlitchnyi V, Meyer O and Dobbek H (2006) Structural insights into methyltransfer reactions of a corrinoid iron-sulfur protein involved in acetyl-CoA synthesis. Proceedings of the National Academy of Sciences of the USA 103: 14331–14336.

Related Sub-Topics:

Protein Structure | Other Biomolecules: Structure, Function, Metabolism | Enzymes: Structure and Action Mechanism
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Article Title: Cobalamin Coenzymes and Vitamin B12
 
How to Cite close
Buckel, Wolfgang(Sep 2007) Cobalamin Coenzymes and Vitamin B12. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000666.pub2]