Entry
Name
cyanocobalamin reductase;
MMACHC (gene name);
CblC;
cyanocobalamin reductase (NADPH, cyanide-eliminating);
cyanocobalamin reductase (NADPH, CN-eliminating);
NADPH:cyanocob(III)alamin oxidoreductase (cyanide-eliminating);
cob(I)alamin, cyanide:NADP+ oxidoreductase;
cyanocobalamin reductase (cyanide-eliminating)
Class
Oxidoreductases;
Oxidizing metal ions;
With NAD+ or NADP+ as acceptor
BRITE hierarchy
Sysname
cob(II)alamin, hydrogen cyanide:NADP+ oxidoreductase
Reaction(IUBMB)
2 cob(II)alamin-[cyanocobalamin reductase] + 2 hydrogen cyanide + NADP+ = 2 cyanocob(III)alamin + 2 [cyanocobalamin reductase] + NADPH + H+ [RN:
R02999 ]
Reaction(KEGG)
Substrate
cob(II)alamin-[cyanocobalamin reductase];
hydrogen cyanide [CPD:
C01326 ];
NADP+ [CPD:
C00006 ]
Product
cyanocob(III)alamin [CPD:
C02823 ];
[cyanocobalamin reductase];
NADPH [CPD:
C00005 ];
H+ [CPD:
C00080 ]
Comment
The mammalian enzyme, which is cytosolic, can bind internalized cyanocobalamin and process it to cob(II)alamin by removing the upper axial ligand. The product remains bound to the protein, which, together with its interacting partner MMADHC, transfers it directly to downstream enzymes involved in adenosylcobalamin and methylcobalamin biosynthesis. In addition to its decyanase function, the mammalian enzyme also catalyses an entirely different chemical reaction with alkylcobalamins, using the thiolate of glutathione for nucleophilic displacement, generating cob(I)alamin and the corresponding glutathione thioether (cf. EC
2.5.1.151 , alkylcobalamin dealkylase).
History
EC 1.16.1.6 created 1989 as EC 1.6.99.12, transferred 2002 to EC 1.16.1.6, modified 2018, modified 2021
Pathway
Orthology
K14618 cyanocobalamin reductase (cyanide-eliminating) / alkylcobalamin dealkylase
Genes
PANU : 100999738(MMACHC) 101002954
PROB : 127225222(Mmachc) 127226849
CCAN : 109686603 109701349
ITI : 101960457 101970295(Mmachc)
MLK : 131809126(MMACHC) 131835548
CCAD : 122436862 122437053(MMACHC)
MBEZ : 129540835(MMACHC) 129550023
PBRV : 138165026 138165396
PPOI : 119105643 119106005
CSCU : 111617610 111620357
PMEO : 129597649 129601735
CEL : CELE_ZK546.17(cblc-1)
CRQ : GCK72_005924 GCK72_005926
LSAX : 138965880 138967098
CVN : 111111573 111113637 111113640 111113864 111113890 111115724 111115983 111115984 111120938
DPOL : 127843831 127845655
OBI : 106878149 106878150 106878154 106880449
EHX : EMIHUDRAFT_460327 EMIHUDRAFT_465565
» show all
Taxonomy
Reference
Authors
Watanabe F, Oki Y, Nakano Y, Kitaoka S.
Title
Occurrence and characterization of cyanocobalamin reductase (NADPH; CN-eliminating) involved in decyanation of cyanocobalamin in Euglena gracilis.
Journal
Reference
Authors
Kim J, Gherasim C, Banerjee R
Title
Decyanation of vitamin B12 by a trafficking chaperone.
Journal
Reference
Authors
Koutmos M, Gherasim C, Smith JL, Banerjee R
Title
Structural basis of multifunctionality in a vitamin B12-processing enzyme.
Journal
Reference
Authors
Mah W, Deme JC, Watkins D, Fung S, Janer A, Shoubridge EA, Rosenblatt DS, Coulton JW
Title
Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B(12) metabolism.
Journal
Other DBs
ExplorEnz - The Enzyme Database: 1.16.1.6
ExPASy - ENZYME nomenclature database: 1.16.1.6