MMACHC dealkylates RCbl

Stable Identifier
Reaction [transition]
Homo sapiens
an R-cob(III)alamin + apo--(alkylcobalamin reductase) + glutathione => an S-substituted glutathione + cob(I)alamin--(alkylcobalamin reductase) + H(+)
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

MMACHC (Methylmalonic aciduria and homocystinuria type C protein, aka cblC protein) catalyses the removal of the "R" group (formally, the upper axial ligand) from RCbl (eg dealkylation of AdoCbl and MeCbl) coupled to its reduction to cob(I)alamin (+1 oxidation state) (Hannibal et al. 2009; Kim et al. 2009; Koutmos et al. 2011).

Defects in MMACHC cause methylmalonic aciduria and homocystinuria type cblC (MMAHCC; MIM:277400). MMAHCC is the most common disorder of Cbl metabolism and is characterised by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, haematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings (Lerner Ellis et al. 2006).

Literature References
PubMed ID Title Journal Year
16311595 Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type

Dobson, CM, Doré, C, Pawelek, PD, Gravel, RA, Morel, CF, Rosenblatt, DS, Rommens, JM, Lepage, P, Dunbar, GV, Hosack, AR, Shoubridge, EA, Forgetta, V, Watkins, D, Antonicka, H, Morgan, K, Leclerc, D, Moras, E, Coulton, JW, Tirone, JC, Lerner-Ellis, JP, Fujiwara, TM, Atkinson, JL

Nat. Genet. 2006
19447654 Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product

Hannibal, L, Rosenblatt, DS, Kim, J, Wang, S, Banerjee, R, Jacobsen, DW, Brasch, NE

Mol. Genet. Metab. 2009
19801555 A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins

Hannibal, L, Kim, J, Gherasim, C, Banerjee, R, Jacobsen, DW

J Biol Chem 2009
21697092 Structural basis of multifunctionality in a vitamin B12-processing enzyme

Koutmos, M, Smith, JL, Gherasim, C, Banerjee, R

J Biol Chem 2011
Catalyst Activity

oxidoreductase activity of MMACHC [cytosol]

Orthologous Events
Cite Us!