Reactome | MMACHC dealkylates RCbl

MMACHC dealkylates RCbl

Stable Identifier

R-HSA-3095889

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

an R-cob(III)alamin + apo--(alkylcobalamin reductase) + glutathione => an S-substituted glutathione + cob(I)alamin--(alkylcobalamin reductase) + H(+)

ReviewStatus

5/5

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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