Reaction: (1) methylcob(III)alamin + [alkylcobalamin dealkylase] + glutathione = cob(I)alamin-[alkylcobalamin dealkylase] + an S-methyl glutathione
(2) adenosylcob(III)alamin + [alkylcobalamin dealkylase] + glutathione = cob(I)alamin-[alkylcobalamin dealkylase] + S-adenosyl glutathione
Other name(s): MMACHC (gene name); alkylcobalamin:glutathione S-alkyltransferase; alkylcobalamin reductase
Systematic name: methylcobalamin:glutathione S-methyltransferase
Comments: This mammalian enzyme, which is cytosolic, can bind internalized methylcob(III)alamin and adenosylcob(III)alamin and process them to cob(I)alamin using the thiolate of glutathione for nucleophilic displacement. The product remains bound to the protein, and, following its oxidation to cob(II)alamin, is transferred by the enzyme, together with its interacting partner MMADHC, directly to downstream enzymes involved in adenosylcob(III)alamin and methylcob(III)alamin biosynthesis. In addition to its dealkylase function, the enzyme also catalyse an entirely different decyanase reaction with cyanocob(III)alamin (cf. EC 1.16.1.6, cyanocobalamin reductase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Hannibal, L., Kim, J., Brasch, N.E., Wang, S., Rosenblatt, D.S., Banerjee, R. and Jacobsen, D.W. Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Mol. Genet. Metab. 97 (2009) 260-266. [PMID: 19447654]
2. Kim, J., Hannibal, L., Gherasim, C., Jacobsen, D.W. and Banerjee, R. A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins. J. Biol. Chem. 284 (2009) 33418-33424. [PMID: 19801555]
3. Koutmos, M., Gherasim, C., Smith, J.L. and Banerjee, R. Structural basis of multifunctionality in a vitamin B12-processing enzyme. J. Biol. Chem. 286 (2011) 29780-29787. [PMID: 21697092]