Disease relevance of MMAA

• In Methylobacterium extorquens AM1, a mutant defective in the MMAA homolog meaB was unable to grow on C(1) and C(2) compounds because of the inability to convert methylmalonyl-CoA to succinyl-CoA (Korotkova N., Chistoserdova, L., Kuksa, V., and Lidstrom, M. E. (2002) J. Bacteriol. 184, 1750-1758) [1].

High impact information on MMAA

• There were highly significant differences in plasma concentrations and activities of paraoxonase between genotypes defined by the 54 polymorphism: MMAA, MLAA, LLAA; protein, 65.3+/-18.0, 77.9+/-18.0, 93.5+/-26.0 microg/ml; P < 0.0001: activity (phenylacetate), 48.6+/-13.5, 64.1+/-14.5, 68.1+/-13.0 U/ml; P < 0.0001 [2].
• A patient, formerly identified as belonging to the cblA complementation group of vitamin B12 disorders but lacking mutations in the affected gene, MMAA, was tested for mutations in the MCEE gene [3].
• In the MMAA patients analyzed, frameshift mutations are prevalent [4].
• The MMAA protein likely transports Cbl into the mitochondria for adenosylcobalamin synthesis, while the MMAB protein appears to be an adenosyltransferase [5].
• When human alveolar epithelial type II (L-132) cells in culture were exposed to either one of these three arsenic compounds, DNA single-strand breaks resulting from the inhibition of repair polymerization were remarkably produced by exposure to DMAA at 5 to 100 microM, while not by that to ARS and MMAA even at 100 microM [6].

Biological context of MMAA

• Genomic DNA from 37 cblA patients, diagnosed on the basis of cellular adenosylcobalamin synthesis, methylmalonyl-coenzyme A (CoA) mutase function, and complementation analysis, was analyzed for deleterious mutations in the MMAA gene by DNA sequencing of exons and flanking sequences [7].
• Mutations in the MMAA gene on human chromosome 4q31.21 result in vitamin B12-responsive methylmalonic aciduria (cblA complementation group) due to deficiency in the synthesis of adenosylcobalamin [7].
• When L-132 cells were exposed to 100 microM MMAA in the presence of 10 mM S-adenosyl-L-methionine (SAM), which is a well-known methyl-group donor in metabolic methylation of arsenics, DNA repair synthesis was induced along with an increase in the amount of dimethylarsenic in the cells [6].
• In 160 subjects with no occupational exposure to arsenic compounds, InAs , MMAA , DMAA each accounted for about 10% of the total arsenic urinary excretion (17.2 +/- 11.1 micrograms/1), thus indicating that in the normal population over 60% of arsenic in urine is present in other organic forms [8].

Associations of MMAA with chemical compounds

• The total content of arsenic and of its inorganic (As(III) and As(V)) and organic (monomethylarsonic acid, MMAA, and dimethylarsinic acid, DMAA) species were determined in a set of 21 alcoholic and alcohol-free beer samples using the technique of Hydride Generation Atomic Absorption Spectrometry [9].
• A 4 x 3 factorial experiment was conducted with four As species [arsenite, arsenate, methylarsonic acid (MMAA), dimethylarsinic acid (DMAA)] and three As concentrations (1.0, 2.0, and 5.0 mg L(-)(1)) [10].
• Organic arsenicals, especially MMAA, were clearly phytotoxic to this turnip cultivar [10].
• The mobile phase containing 2 mM NaH(2)PO(4) and 0.2 mM EDTA at pH 6 allowed adequate separation of four As species (As(III), As(V), MMAA, DMAA) in less than 10 min [11].

References