Abstract
MMA may be caused by at least three different enzyme defects: l)Defect of methylmalonyl-CoA(MMCoA)mutase-apoenzyme; 2)Defective metabolism or transport of the coenzyme of MMCoA mutase, 5'-deoxyadenosylcobalamin(dA-Bl2), or of its precursor, vitamin B12; 3) Deficiency of MMCoA racemase. -We have studied methylmalonate metabolism in leucocytes and cultured skin fibroblasts of 5 p. with MMA (1 p.B12-responsive, 4 p. clinically non-responsive). Intact fibroblasts of all 5 p. failed to metabolize 2-methyl-14C-malonate (MM-14C)to 14CO2, whether or not vitamin B12 or dA-B12 (10−5M) were added; whereas in intact leucocytes of the 3 p. so far investigated, 14CO2 formation from MM-14C was always present and similar to controls. Disrupted fibroblasts were studied using a specific enzyme assay with propionyl-CoA and NaH14CO3 as substrates. Methylmalonate metabolism was absent or severely impaired in all p. as revealed by methylmalonate accumulation and succinate formation. While addition of vitamin B12 (10−11 to 10−5M) had no effect in any of the p., addition of dA-B12 (10−7 to 10−5M) did not enhance succinate formation in 2 p., but fully restored enzyme activity in 2 other p. These data suggest a defective metabolism rather than a defective transport mechanism of the B12-coenzyme in the latter 2 p.
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Baumgartner, R., Bachmann, C. & Stalder, G. Methylmalonic acidemia (MMA):Enzymatic studies in 5 non-related patients. Pediatr Res 8, 906 (1974). https://doi.org/10.1203/00006450-197411000-00061
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DOI: https://doi.org/10.1203/00006450-197411000-00061
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