Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-chain acyl-CoA dehydrogenase deficiency is an inherited metabolic disorder biochemically characterized by tissue accumulation of ethylmalonic (EMA) and methylsuccinic (MSA) acids and clinically by severe neurological symptoms. In the present study we investigated the in vitro effects of EMA and MSA on the activity of creatine kinase (CK) in homogenates from cerebral cortex, skeletal and cardiac muscle of rats. EMA significantly inhibited CK activity from cerebral cortex, but did not affect this activity in skeletal and cardiac muscle. Furthermore, MSA had no effect on this enzyme in all tested tissues. Glutathione (GSH), ascorbic acid and alpha-tocopherol, and the nitric oxide synthase inhibitor L-NAME, did not affect the enzyme activity per se, but GSH fully prevented the inhibitory effect of EMA when co-incubated with EMA. In contrast, alpha-tocopherol, ascorbic acid and L-NAME did not influence the inhibitory effect of the acid. The data suggest that inhibition of brain CK activity by EMA is possibly mediated by oxidation of essential groups of the enzyme, which are protected by the potent intracellular, endogenous, naturally occurring antioxidant GSH.
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PMID:Inhibition of creatine kinase activity in vitro by ethylmalonic acid in cerebral cortex of young rats. 1251 16

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an inherited metabolic disorder biochemically characterized by tissue accumulation of predominantly ethylmalonic acid (EMA) and clinically by neurological dysfunction. In the present study we investigated the in vitro effects of EMA on the activity of the mitochondrial (Mi-CK) and cytosolic (Cy-CK) creatine kinase isoforms from cerebral cortex, skeletal muscle, and cardiac muscle of young rats. CK activities were measured in the mitochondrial and cytosolic fractions prepared from whole-tissue homogenates of 30-day-old Wistar rats. The acid was added to the incubation medium at concentrations ranging from 0.5 to 2.5 mM. EMA had no effect on Cy-CK activity, but significantly inhibited the activity of Mi-CK at 1.0 mM and higher concentrations in the brain. In contrast, both Mi-CK and Cy-CK from skeletal muscle and cardiac muscle were not affected by the metabolite. We also evaluated the effect of the antioxidants glutathione (GSH), ascorbic acid, and alpha-tocopherol and the nitric oxide synthase inhibitor L-NAME on the inhibitory action of EMA on cerebral cortex Mi-CK activity. We observed that the drugs did not modify Mi-CK activity per se, but GSH and ascorbic acid prevented the inhibitory effect of EMA when co-incubated with the acid. In contrast, L-NAME and alpha-tocopherol could not revert the inhibition provoked by EMA on Mi-CK activity. Considering the importance of CK for brain energy homeostasis, it is proposed that the inhibition of Mi-CK activity may be associated to the neurological symptoms characteristic of SCAD deficiency.
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PMID:Ethylmalonic acid inhibits mitochondrial creatine kinase activity from cerebral cortex of young rats in vitro. 1271 29