Disease relevance of Methylmalonic acid

• Urinary methylmalonic acid to detect vitamin B12 deficiency [1].
• Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of methylmalonic acid while free of hematologic and neurologic abnormalities [2].
• There were no correlations between SAM or SAH concentrations or methylation ratio and age or sex in both groups, or serum B12 and folate concentrations, CSF folate, serum or CSF methylmalonic acid, risk factors, body mass index, specific drug treatment received, or disease stage in the HIV group [3].
• This study shows that methylmalonyl-CoA mutase is induced by several stresses, including ischemia, and would serve to decrease the accumulation of an endogenous cellular mitochondrial inhibitor and neurotoxin, methylmalonic acid [4].
• Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians [5].

Psychiatry related information on Methylmalonic acid

• Hyperammonemia is a common finding in children with methylmalonic acidemia, an inherited metabolic disease characterized by mental retardation, convulsions, and accumulation of methylmalonic acid (MMA) [6].
• Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease [7].
• Cobalamin, folate, methylmalonic acid, homocysteine, and gastritis markers in dementia [8].
• Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis [9].
• We observed that rats chronically injected with methylmalonic acid (MA), although presenting no alterations in the acquisition phase, showed a long lasting reversal learning impairment [10].

High impact information on Methylmalonic acid

• Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31) [11].
• We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients [11].
• Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day) [12].
• Elevated concentrations of methylmalonic acid were also found in amniotic fluid and maternal urine [13].
• In all participants with vitamin B12 deficiency who received treatment (15 of 21), methylmalonic acid and total homocysteine levels decreased substantially, confirming the deficiency before treatment [14].

Chemical compound and disease context of Methylmalonic acid

• Elevated methylmalonic acid and total homocysteine levels show high prevalence of vitamin B12 deficiency after gastric surgery [14].
• Severe toxicity from pemetrexed-based therapy has become more predictable using the vitamin deficiency marker homocysteine and, to a lesser extent, methylmalonic acid [15].
• It appears that hypothyroidism, induced either by thyroidectomy or by feeding thiouracil, slows the rate of depletion of hepatic B-12 which in turn facilitates the metabolism of methylmalonic acid and decreases its excretion in the urine [16].
• DESIGN AND INTERVENTIONS: We examined 937 individuals not treated with vitamin B12 but in whom vitamin B12 deficiency was suspected because of a plasma methylmalonic acid (MMA) above 0.28 micromol L(-1) within the past 4 years [17].
• Urinary methylmalonic acid/creatinine ratio: a gold standard test for tissue vitamin B12 deficiency [18].

Biological context of Methylmalonic acid

• Treatment during the last nine weeks of gestation with large doses of vitamin B12 given to the mother reversed the increasing maternal excretion of methylmalonic acid, which was 23 mug per milligram of creatinine at 31 weeks' gestation [13].
• Methylmalonic acid, which is formed from the MCM substrate methylmalonyl-CoA and which inhibits succinate dehydrogenase (SDH), produced dose-related cell death when injected into the basal ganglia of adult rat brain [4].
• It has become the subject of intense debates whether methylmalonic acid is the major toxin, inhibiting respiratory chain complex II [19].
• Cobalamin deficiency in general practice. Assessment of the diagnostic utility and cost-benefit analysis of methylmalonic acid determination in relation to current diagnostic strategies [20].
• Methylmalonic acidemia is an inherited metabolic disorder that leads to brain damage associated to the accumulation of methylmalonic acid (MMA) and impairment of energy metabolism [21].

Anatomical context of Methylmalonic acid

• To elucidate whether methylmalonic acid is a respiratory chain inhibitor, we used spectrophotometric analysis of complex II activity in submitochondrial particles from bovine heart, radiometric analysis of 14C-labeled substrates (pyruvate, malate, succinate), and analysis of ATP production in muscle from mice [19].
• Cerebrospinal fluid methylmalonic acid levels in normal subjects and patients with cobalamin deficiency [22].
• Urinary methylmalonic acid excretion in infants fed formula or human milk [23].
• Intrastriatal methylmalonic acid administration induces convulsions and TBARS production, and alters Na+,K+-ATPase activity in the rat striatum and cerebral cortex [24].
• The observations suggest that methylmalonic acid is inhibitory to the proliferation of marrow stem cells [25].

Associations of Methylmalonic acid with other chemical compounds

• At birth the methylmalonic acid content of the baby's urine (67 mug per milligram of creatinine) and serum (2.0 mug per milliliter) was only moderately elevated, and serum vitamin B12 concentration was very high [13].
• Studies of urine obtained from normal subjects (by isolation, partial purification, and then assay by the isotope dilution technique) demonstrated urinary excretion of less than 1 mg of propionic acid and 1-5 mg of methylmalonic acid per day [26].
• We also investigated the relationship between these proteins and concentrations of methylmalonic acid (MMA), the functional marker of vitamin B12 status [27].
• We measured HCY, methylmalonic acid (MMA), and cystathionine by gas chromatography-mass spectrometry; S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) by liquid chromatography-tandem mass spectrometry; and the B-vitamins by HPLC or immunoassays [28].
• No significant association was found between depression and plasma vitamin B12 (p=0.13), plasma methylmalonic acid (p=0.67), erythrocyte folate (p=0.77), and plasma total homocysteine (p=0.16) [29].

Gene context of Methylmalonic acid

• We demonstrated that pre-treatment of cerebral cortex slices of young rats with 2.5 mM buffered methylmalonic acid (MMA) is effective in decreasing in vitro incorporation of [32P]ATP into neurofilament subunits (NF-M and NF-L) and alpha- and beta-tubulins [30].
• RNA interference against mmcm-1, mmab-1, mmaa-1 in the presence of propionic acid revealed a chemical phenotype of increased methylmalonic acid; deletion mutants of mmcm-1, mmab-1 and mce-1 displayed reduced 1-[(14)C]-propionate incorporation into macromolecules [31].
• Methylmalonic acid revealed no direct effects on the respiratory chain function, i.e. on single electron transferring complexes I-IV, ATPase, and mitochondrial transporters [19].
• Rabbits injected with pure human placental transcobalamin II-receptor (TC II-R) failed to thrive with no apparent tissue or organ damage, but a 2-fold elevation of the metabolites, homocysteine, methylmalonic acid, and the ligand, transcobalamin II, in their plasma [32].
• In contrast, in six patients with elevated serum methylmalonic acid levels due to renal failure, CSF concentrations were normal in five and the CSF: serum ratio was less than one in four [22].

Analytical, diagnostic and therapeutic context of Methylmalonic acid

• Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing [33].
• Vitamin B12 deficiency is estimated to affect 10%-15% of people over the age of 60, and the laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels [34].
• PURPOSE: This study assesses the value of the urinary methylmalonic acid (MMA) assay by gas chromatography mass spectrometry as a screening procedure for detection of cobalamin (Cbl) deficiency and estimates the prevalence of undetected Cbl deficiency in elderly populations [35].
• Automated assay of methylmalonic acid in serum and urine by derivatization with 1-pyrenyldiazomethane, liquid chromatography, and fluorescence detection [36].
• Application of capillary electrophoresis with laser-induced fluorescence detection for routine determination of methylmalonic acid in human serum [37].

References