Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethylmalonic aciduria is a common finding in patients affected by short-chain acyl-CoA dehydrogenase (SCAD) deficiency and other diseases characterized by encephalopathy, muscular symptomatology, and lactic acidemia. Considering that the pathophysiological mechanisms of these disorders are practically unknown and that lactic acidosis suggest an impairment of energy production, the objective of the present work was to investigate the in vitro effect of ethylmalonic acid (EMA), at concentrations varying from 0.25 to 5.0 mM, on important parameters of energy metabolism in human skeletal muscle, such as the activities of the respiratory chain complexes and of creatine kinase, which are responsible for most of the ATP produced and transferred inside the cell. We verified that EMA significantly inhibited the activity of complex I-III at concentrations as low as 0.25 mM, complex II-III at 1 mM and higher concentrations, and complex II at the concentration of 5 mM. In contrast, complex IV was not inhibited by the acid. Finally, we observed that the activity of creatine kinase was significantly inhibited by EMA at the concentrations of 1 and 5 mM. These results suggest that EMA compromises energy metabolism in human skeletal muscle. In case the in vitro effects detected in the present study also occur in vivo, it is tempting to speculate that they may contribute, at least in part, to explain the hypotonia/myopathy, as well as the increased concentrations of lactic acid present in the patients affected by illnesses in which EMA accumulates.
 ...
PMID:Inhibition of the electron transport chain and creatine kinase activity by ethylmalonic acid in human skeletal muscle. 1677 66

Two genetically different pig breeds, the Korean native pig (KNP) and the Western meat-producing Landrace, show breed-specific traits in stress responsiveness (stress hormone levels), growth performance (live weight), and meat quality (intramuscular fat content). We analyzed expression levels within the proteome and transcriptome of the longissimus muscles of both breeds using two-dimensional electrophoresis (2-DE) and microarray analysis. We constructed a porcine proteome database focused mainly on mitochondrial proteins. In total, 101 proteins were identified, of which approximately 60% were metabolic enzymes and mitochondrial proteins. We screened several proteins and genes related to stress and metabolism in skeletal muscles using comparative analysis. In particular, three stress-related genes (heat shock protein beta-1, stress-70 protein, and heat shock 70 kDa protein) were more highly expressed in the Landrace than in the KNP breed. Six metabolism-related genes (peroxisome proliferative activated receptor alpha, short-chain acyl-CoA dehydrogenase, succinate dehydrogenase, NADH-ubiquinone oxidoreductase, glycerol-3-phosphate dehydrogenase, and sterol regulatory element binding protein-1c), all of which are involved in energy and lipid metabolism, were more highly expressed at the protein or mRNA level in the KNP breed. These data may reflect the breed dependence of traits such as stress responsiveness, growth performance, and meat quality.
 ...
PMID:Comparative studies of skeletal muscle proteome and transcriptome profilings between pig breeds. 2053 84

Tissue accumulation and high urinary excretion of ethylmalonic acid (EMA) occur in ethylmalonic encephalopathy (EE) and short chain acyl-CoA dehydrogenase deficiency (SCADD). Although these autosomal recessive disorders are clinically characterized by neurological abnormalities, the mechanisms underlying the brain damage are poorly known. Considering that little is known about the neurotoxicity of EMA and that hyperlacticacidemia occurs in EE and SCADD, we evaluated the effects of this metabolite on important parameters of oxidative metabolism in isolated rat brain mitochondria. EMA inhibited either ADP-stimulated or uncoupled mitochondrial respiration supported by succinate and malate, but not by glutamate plus malate. In addition, EMA mildly stimulated oxygen consumption by succinate-respiring mitochondria in resting state. Methylmalonic acid (MMA), malonic acid (MA) and butylmalonic acid (BtMA) had a similar effect on ADP-stimulated or uncoupled respiration. Furthermore, EMA-, MMA- and BtMA-induced inhibitory effects on succinate oxidation were significantly minimized by nonselective permeabilization of the mitochondrial membranes by alamethicin, whereas MA inhibitory effect was not altered. In addition, MA was the only tested compound that reduced succinate dehydrogenase activity. We also observed that EMA markedly inhibited succinate and malate transport through the mitochondrial dicarboxylate carrier. Mitochondrial membrane potential was also reduced by EMA and MA, but not by MMA, using succinate as electron donor, whereas none of these compounds was able to alter the membrane potential using glutamate plus malate as electron donors. Taken together, our results strongly indicate that EMA impairs succinate and malate uptake through the mitochondrial dicarboxylate carrier.
 ...
PMID:Ethylmalonic acid impairs brain mitochondrial succinate and malate transport. 2213 2