Defective MMADHC does not bind MMACHC:B12r

Stable Identifier
R-HSA-3318571
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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MMACHC:B12r (cob(II)alamin, vitamin B12r) binding to methylmalonic aciduria and homocystinuria type D protein (MMADHC) represents a branch point in the targeted delivery of B12r to either cytosolic or mitochondrial enzymes requiring this cofactor (Mah et al. 2013, Plesa et al. 2011, Deme et al. 2012). Both MMACHC and MMADHC are implicated in the intracellular transport of cobalamins but exact details of the mechanisms involved remain unclear.

Defects in MMADHC cause methylmalonic aciduria and homocystinuria type cblD (MMAHCD; MIM:277410), a disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) (Coelho et al. 2008). There are 3 biochemical phenotypes for this disorder; sufferers with homocystinuria (mutants L259P, T182N and Y249C), methylmalonic aciduria (mutants S20*, and R54*), and combined homocystinuria and methylmalonic aciduria (mutants R250* and Y140*) (Coelho et al. 2008, Suormala et al. 2004).

Literature References
PubMed ID Title Journal Year
18385497 Gene identification for the cblD defect of vitamin B12 metabolism

Coelho, D, Suormala, T, Stucki, M, Lerner-Ellis, JP, Rosenblatt, DS, Newbold, RF, Baumgartner, MR, Fowler, B

N. Engl. J. Med. 2008
21071249 Interaction between MMACHC and MMADHC, two human proteins participating in intracellular vitamin B?? metabolism

Plesa, M, Kim, J, Paquette, SG, Gagnon, H, Ng-Thow-Hing, C, Gibbs, BF, Hancock, MA, Rosenblatt, DS, Coulton, JW

Mol. Genet. Metab. 2011
15292234 The cblD defect causes either isolated or combined deficiency of methylcobalamin and adenosylcobalamin synthesis

Suormala, T, Baumgartner, MR, Coelho, D, Zavadakova, P, Kozich, V, Koch, HG, BerghaĆ¼ser, M, Wraith, JE, Burlina, A, Sewell, A, Herwig, J, Fowler, B

J. Biol. Chem. 2004
23270877 Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B(12) metabolism

Mah, W, Deme, JC, Watkins, D, Fung, S, Janer, A, Shoubridge, EA, Rosenblatt, DS, Coulton, JW

Mol. Genet. Metab. 2013
22832074 Structural features of recombinant MMADHC isoforms and their interactions with MMACHC, proteins of mammalian vitamin B12 metabolism

Deme, JC, Miousse, IR, Plesa, M, Kim, JC, Hancock, MA, Mah, W, Rosenblatt, DS, Coulton, JW

Mol. Genet. Metab. 2012
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
methylmalonic aciduria and homocystinuria type cblD 0050716 Cobalamin D deficiency
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