MMACHC reduces Cbl

Stable Identifier
Reaction [transition]
Homo sapiens
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Methylmalonic aciduria and homocystinuria type C protein (MMACHC aka cblC protein) is suggested to be involved in the binding and intracellular transport of cobalamin (Cbl aka vitamin B12). MMACHC can catalyse the removal of the "R" group (formally called the upper axial ligand) from Cbl (eg dealkylation of AdoCbl and MeCbl or decyanation of CNCbl) which can result in the reduction of Cbl (+3 oxidation state) to cob(II)alamin (B12r, vitamin B12r +2 oxidation state) (Hannibal et al. 2009). Cob(II)alamin is escorted by MMACHC to its destination enzyme partners in the mitochondria and cytosol.

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

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

Mol. Genet. Metab. 2009
16311595 Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type

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

Nat. Genet. 2006
Catalyst Activity

oxidoreductase activity of MMACHC [cytosol]

Orthologous Events
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