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Information on EC 2.5.1.151 - alkylcobalamin dealkylase and Organism(s) Homo sapiens and UniProt Accession Q9Y4U1
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2.5.1.151 alkylcobalamin dealkylaseIUBMB 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).
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Word Map
- 2.5.1.151
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methylmalonic
- homocystinuria
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inborn
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acidemia
- homocysteine
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late-onset
- betaine
- adenosylcobalamin
- hyperhomocysteinemia
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mecbl
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mmadhcs
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c.271dupa
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adocbl
- propionylcarnitine
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homocysteinemia
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decyanation
- cyanocobalamin
- hydroxycobalamin
- mmaa
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epimutation
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megaloblastic
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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[alkylcobalamin dealkylase]
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cob(I)alamin-[alkylcobalamin dealkylase]
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=
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[alkylcobalamin dealkylase]
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=
cob(I)alamin-[alkylcobalamin dealkylase]
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Synonyms
mmachc, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alkylcobalamin reductase
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alkylcobalamin:glutathione S-alkyltransferase
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MMACHC
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SYSTEMATIC NAME
IUBMB Comments
methylcobalamin:glutathione S-methyltransferase
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).
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5'-deoxyadenosylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-5'-deoxyadenosylglutathione
an alkylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + an S-alkylglutathione
butyrylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-butyrylglutathione
ethylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-ethylglutathione
hexylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-hexylglutathione
methylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-methylglutathione
pentylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-pentylglutathione
propylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-propyglutathione
5'-deoxyadenosylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-5'-deoxyadenosylglutathione
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-
-
?
5'-deoxyadenosylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-5'-deoxyadenosylglutathione
the enzyme can bind internalized alkylcobalamins 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 (a cytosolic cobalamin trafficking chaperone), directly to downstream enzymes involved in adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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-
?
an alkylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + an S-alkylglutathione
the CblC protein is responsible for alkylcobalamins dealkylation in mammalian cells
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-
?
an alkylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + an S-alkylglutathione
the enzyme is involved in the cobalamin-processing pathway. It acts as a a cytosolic cobalamin trafficking chaperone
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-
?
butyrylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-butyrylglutathione
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-
-
?
butyrylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-butyrylglutathione
the enzyme can bind internalized alkylcobalamins 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 adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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-
?
ethylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-ethylglutathione
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-
-
?
ethylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-ethylglutathione
the enzyme can bind internalized alkylcobalamins 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 adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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-
?
hexylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-hexylglutathione
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-
-
?
hexylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-hexylglutathione
the enzyme can bind internalized alkylcobalamins 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 adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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-
?
methylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-methylglutathione
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?
methylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-methylglutathione
the enzyme can bind internalized alkylcobalamins 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 adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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-
?
pentylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-pentylglutathione
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-
-
?
pentylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-pentylglutathione
the enzyme can bind internalized alkylcobalamins 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 adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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-
?
propylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-propyglutathione
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-
-
?
propylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + S-propyglutathione
the enzyme can bind internalized alkylcobalamins 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 adenosylcobalamin and methylcobalamin biosynthesis. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione
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?
additional information
?
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in addition to its dealkylase function, the enzyme also catalyses a decyanase reaction with cyanocobalamin, cf. EC 1.16.1.6, cyanocobalamin reductase (cyanide-eliminating)
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?
additional information
?
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in addition to its dealkylase function, the enzyme also catalyses a decyanase reaction with cyanocobalamin, cf. EC 1.16.1.6, cyanocobalamin reductase (cyanide-eliminating)
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
an alkylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + an S-alkylglutathione
an alkylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + an S-alkylglutathione
the CblC protein is responsible for alkylcobalamins dealkylation in mammalian cells
-
-
?
an alkylcobalamin + [alkylcobalamin reductase] + glutathione
cob(I)alamin-[alkylcobalamin reductase] + an S-alkylglutathione
the enzyme is involved in the cobalamin-processing pathway. It acts as a a cytosolic cobalamin trafficking chaperone
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the enzyme also catalyzes the reductive decyanation of cyanocob(III)alamin in the presence of FMN/FAD and NADPH, cf. EC 1.16.1.6, cyanocobalamin reductase (cyanide-eliminating)
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
evolution
in addition to its dealkylase function, the enzyme also catalyses a decyanase reaction with cyanocobalamin, cf. EC 1.16.1.6, cyanocobalamin reductase (cyanide-eliminating). The enzyme represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries
evolution
the enzyme does not appear to be a sequence relative of either enzyme class and may have arisen by convergent evolution
metabolism
together with its interacting partner MMADHC, the enzyme is involved in vitamin B12 metabolism. The function of MMADHC is exerted through its structured C-terminal domain via interactions with MMACHC
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MMAC_HUMAN
282
0
31728
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28900
His-tagged recombinant truncated human protein (t-CblC), t-CblC is the predominant, if not only, form of CblC
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallization of apo- and cobalamin-bound forms, cocrystallization of truncated CblCDELTAC44 with methylcobalamin, vapor diffusion method
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kim, J.; Hannibal, L.; Gherasim, C.; Jacobsen, D.W.; Banerjee, R.
A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins
J. Biol. Chem.
284
33418-33424
2009
Homo sapiens (Q9Y4U1), Homo sapiens
Koutmos, M.; Gherasim, C.; Smith, J.; Banerjee, R.
Structural basis of multifunctionality in a vitamin B 12-processing enzyme
J. Biol. Chem.
286
29780-29787
2011
Homo sapiens (Q9Y4U1)
Deme, J.C.; Miousse, I.R.; Plesa, M.; Kim, J.C.; Hancock, M.A.; Mah, W.; Rosenblatt, D.S.; Coulton, J.W.
Structural features of recombinant MMADHC isoforms and their interactions with MMACHC, proteins of mammalian vitamin B12 metabolism
Mol. Genet. Metab.
107
352-362
2012
Homo sapiens (Q9Y4U1), Homo sapiens
Hannibal, L.; Kim, J.; Brasch, N.E.; Wang, S.; Rosenblatt, D.S.; Banerjee, R.; Jacobsen, D.W.
Processing of alkylcobalamins in mammalian cells A role for the MMACHC (cblC) gene product
Mol. Genet. Metab.
97
260-266
2009
Bos taurus (Q5E9C8), Bos taurus, Homo sapiens (Q9Y4U1), Homo sapiens
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