Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of 2-oxo-4-methylpentanoate, 2-oxo-3-methylbutanoate and 2-oxo-3-methylpentanoate on the activity of pyruvate dehydrogenase (EC 1.2.4.1), citrate synthase (EC 4.1.3.7), acetyl-CoA carboxylase, (EC 6.4.1.2) and fatty acid synthetase derived from the brains of 14-day-old rats were investigated. 2. The pyruvate dehydrogenase enzyme activity was competitively inhibited by 2-oxo-3-methylbutanoate with respect to pyruvate with a K(i) of 2.04mm but was unaffected by 2-oxo-4-methylpentanoate or 2-oxo-3-methylpentanoate. 3. The citrate synthase activity was inhibited competitively (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)~7.2mm) and 2-oxo-3-methylbutanoate (K(i)~14.9mm) but not by 2-oxo-3-methylpentanoate. 4. The acetyl-CoA carboxylase activity was not inhibited significantly by any of the 2-oxo acids investigated. 5. The fatty acid synthetase activity was competitively inhibited (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)~930mum) and 2-oxo-3-methylpentanoate (K(i)~3.45mm) but not by 2-oxo-3-methylbutanoate. 6. Preliminary experiments indicate that 2-oxo-4-methylpentanoate and 2-oxo-3-phenylpropionate (phenylpyruvate) significantly inhibit the ability of intact brain mitochondria from 14-day-old rats to oxidize pyruvate. 7. The results are discussed with reference to phenylketonuria and maple-syrup-urine disease. A biochemical mechanism is proposed to explain the characteristics of these diseases.
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PMID:Differential effects of 2-oxo acids on pyruvate utilization and fatty acid synthesis in rat brain. 415 48

When baker's yeast spheroplasts were lysed by mild osmotic shock, practically all of the isopropylmalate isomerase and the beta-isopropylmalate dehydrogenase was released into the 30,000 x g supernatant fraction, as was the cytosol marker enzyme, glucose-6-phosphate dehydrogenase. alpha-Isopropylmalate synthase, however, was not detected in the initial supernatant, but could be progressively solubilized by homogenization, appearing more slowly than citrate synthase but faster than cytochrome oxidase. Of the total glutamate-alpha-ketoisocaproate transaminase activity, approximately 20% was in the initial soluble fraction, whereas solubilization of the remainder again required homogenization of the spheroplast lysate. Results from sucrose density gradient centrifugation of a cell-free particulate fraction and comparison with marker enzymes suggested that alpha-isopropylmalate synthase was located in the mitochondria. It thus appears that, in yeast, the first specific enzyme in the leucine biosynthetic pathway (alpha-isopropylmalate synthase) is particulate, whereas the next two enzymes in the pathway (isopropylmalate isomerase and beta-isopropylmalate dehydrogenase) are "soluble," with glutamate-alpha-ketoisocaproate transaminase activity being located in both the cytosol and particulate cell fractions.
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PMID:Subcellular localization of the leucine biosynthetic enzymes in yeast. 435 81

Oxidation rates of palmitate (total and antimycin-insensitive), pyruvate, leucine, 4-methyl-2-oxopentanoate and 3-methyl-2-oxobutanoate and activities of two mitochondrial marker enzymes (citrate synthase and cytochrome c oxidase) were assayed in liver and muscle homogenates of fed, clofibrate-treated and 18 hr-starved rats. Significant alterations in the clofibrate-treated and the starved rats were predominantly observed in the liver. Clofibrate feeding increased antimycin-insensitive (peroxisomal) and antimycin-sensitive (mitochondrial) palmitate oxidation and 4-methyl-2-oxopentanoate and pyruvate oxidation in liver. In muscle, only the activities of citrate synthase and cytochrome c oxidase were slightly decreased. Short starvation increased antimycin-sensitive palmitate and 4-methyl-2-oxopentanoate oxidation in liver. The rates of pyruvate and 3-methyl-2-oxobutanoate oxidation were decreased in muscle homogenates. Results suggest that myopathic phenomena observed after chronic clofibrate administration are not related to changes in the capacity of oxidative metabolism of muscle.
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PMID:Effect of clofibrate feeding on palmitate and branched-chain 2-oxo acid oxidation in rat liver and muscle. 631 Dec 21

Assay conditions for measurement of human skin fibroblast branched-chain L-amino acid aminotransferase activity were established and applied to studies on subcellular distribution and kinetic properties of the enzyme. Digitonin fractionation of cultured cells revealed that the aminotransferase activity was mainly (at least about 95%) associated with mitochondrial citrate synthase activity. As tested with L-leucine, activity of the enzyme against amino group acceptors (forward reaction) was in the order 2-oxoglutarate [Symbol: see text] branched-chain > straight-chain 2-oxo acids (C3-C8). With 4-methyl-2-oxopentanoate, activity against amino group donors (reverse reaction) was in the order L-glutamate [Symbol: see text] branched-chain > straight-chain (C2-C6) and other L-amino acids. The data suggest that, in human fibroblasts, isoenzyme type I resides within the mitochondrial space. Possible implications for the metabolism of branched-chain compounds are discussed.
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PMID:Human branched-chain L-amino acid aminotransferase: Activity and subcellular localization in cultured skin fibroblasts. 2417 15