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).
Coelho, D, Suormala, T, Stucki, M, Lerner-Ellis, JP, Rosenblatt, DS, Newbold, RF, Baumgartner, MR, Fowler, B
Plesa, M, Kim, J, Paquette, SG, Gagnon, H, Ng-Thow-Hing, C, Gibbs, BF, Hancock, MA, Rosenblatt, DS, Coulton, JW
Suormala, T, Baumgartner, MR, Coelho, D, Zavadakova, P, Kozich, V, Koch, HG, Berghaüser, M, Wraith, JE, Burlina, A, Sewell, A, Herwig, J, Fowler, B
Mah, W, Deme, JC, Watkins, D, Fung, S, Janer, A, Shoubridge, EA, Rosenblatt, DS, Coulton, JW
Deme, JC, Miousse, IR, Plesa, M, Kim, JC, Hancock, MA, Mah, W, Rosenblatt, DS, Coulton, JW
Loss of function of MMADHC mutants [cytosol]
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