Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoic acid (lip) and 2-oxoglutarate dehydrogenase (sucA) mutants of Escherichia coli K12 exhibit a requirement for exogenous succinate during aerobic growth on glucose minimal medium. Reversion studies have shown that this requirement can be suppressed by gal-linked mutations which inactivate succinate dehydrogenase. Biochemical and genetic studies confirmed that the succinate dehydrogenase gene (sdh) is affected and that suppression is mediated by the same intergenic and indirect mechanism that generates succinate independence in partial revertants of lipoamide dehydrogenase mutants (Creaghan & Guest, 1977). A series of isogenic strains containing all combinations of mutations affecting 2-oxoglutarate dehydrogenase (sucA), succinate dehydrogenase (sdh), isocitrate lyase (aceA) and fumarate reductase (frd) in a background lacking succinate semialdehyde dehydrogenase, was constructed to assess the importance of these enzymes as sources of endogenous succinate (succinyl-CoA) during aerobic and anaerobic growth on glucose. Only strains combining a deficiency in 2-oxoglutarate dehydrogenase with the presence of an active succinate dehydrogenase required succinate for aerobic growth. In all mutants, including the triple mutant (frd sucA aceA), the succinate requirement was suppressed by inactivating succinate dehydrogenase. The aerobic growth rates of succinate-independent strains were most affected by lack of isocitrate lyase but only two mutants (sdh sucA aceA and frd sdh sucA aceA) grew faster with added succinate: the growth yields were lowered by deficiencies in isocitrate lyase and also succinate dehydrogenase. It is concluded that very little succinate is needed for biosynthesis during aerobic growth on glucose and the requirement for relatively high concentrations of succinate (2 mM) by mutants lacking 2-oxoglutarate dehydrogenase or related functions stems from the presence of active succinate dehydrogenase. Anaerobically, either isocitrate lyase or fumarate reductase is essential for succinate-independent growth on glucose.
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PMID:Succinate dehydrogenase-dependent nutritional requirement for succinate in mutants of Escherichia coli K12. 36 70

Skeletal muscles from 12 male, juvenile-onset diabetics (JD) and 13 nondiabetics (ND) were studied to determine the effects of endurance training on mitochondrial enzyme activities, lipoprotein lipase (LPL) activity, and the oxidation of lipids (14C-palmityl CoA) in vitro. Ten weeks of endurance running (30 min/day, 5 days/wk) resulted in 11.0 and 12.9% gains in aerobic capacity for the JD and ND groups (P greater than 0.05), respectively. Both groups showed significant (P less than 0.05) increases in muscle LPL, carnitine palmityl transferase, succinate dehydrogenase, and hexokinase activities with training. Though the pretraining capacities for 14C-palmityl CoA oxidation were similar for both ND and JD groups, the diabetics showed a 41% greater improvement in the measurement of muscle lipid oxidation after training than did the ND group. The principal finding of this research was that skeletal muscle of juvenile diabetics who are in moderate insulin balance shows adaptations to endurance training that are similar to those of nondiabetic men.
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PMID:Training adaptations in skeletal muscle of juvenile diabetics. 46 7

1. Enzyme activities (units/g wet wt.) were determined in the caput and cauda epididymidis and in epididymal spermatozoa of the rat. 2. The activity of most enzymes in the cauda was between 50 and 100% of that in the caput, except that ATP citrate lyase was barely detectable in the cauda. 3. Spermatozoa, unlike epididymal tissue, contained sorbitol dehydrogenase but lacked ATP citrate lyase. NADP+-malate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, succinate dehydrogenase, carnitine acetyltransferase and citrate synthase were 5 to 400 times as active in spermatozoa as in epididymal tissue. 4. 2-Oxoglutarate dehydrogenase was the least active member of the tricarboxylic acid cycle in all tissues and most closely matched the measured flux through the cycle. 5. The concentrations of hydroxyacyl-CoA dehydrogenase and carnitine palmitoyltransferase were equivalent to the more active enzymes of the tricarboxylic acid cycle, indicating the capacity for extensive lipid oxidation, and the presence of 3-hydroxybutyrate dehydrogenase suggests that these tissues can also oxidize ketone bodies. 6. Transfer of reducing equivalents from cytoplasm to mitochondrion is unlikely to occur by means of the glycerol phosphate cycle because mitochondrial glycerol 3-phosphate dehydrogenase is relatively inactive in epididymal tissue, whereas the cytoplasmic enzyme has little activity in spermatozoa, but transfer may be accomplished by the malate-aspartate shuttle. 7. Transfer of acetyl units from mitochondrion to cytoplasm could be effected by the pyruvate-malate cycle in the caput of androgen-maintained rats, but not in the other tissues because of the low activity of ATP citrate lyase. Acetyl unit transfer could take place via acetylcarnitine, mediated by carnitine acetyltransferase. 8. Castration resulted in a decrease in the concentration of nearly all enzymes, although subsequent administration of testosterone restored concentrations to values similar to those in animals maintained by endogenous androgen. The extent to which enzyme concentration was changed by an alteration in androgen status was highly variable, but was most marked in the case of pyruvate carboxylase.
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PMID:Activity and androgenic control of enzymes associated with the tricarboxylic acid cycle, lipid oxidation and mitochondrial shuttles in the epididymis and epididymal spermatozoa of the rat. 72 83

The activities of L-threonine dehydrogenase (I), 2-amino-3-oxybutyrate:CoA ligase (II), malate synthetase (III), isocitrate lyase (IV), glyoxylate dehydrogenase (V), glycine decarboxylase (VI), L-serine hydroxymethyltransferase (VII), glucan synthetase (VIII), glucose 6-phosphate dehydrogenase (IX) and succinic dehydrogenase (X) were detected in cell-free extracts prepared from the mycelium of the fungus Sclerotium rolfsii type R. Transfer of S. rolfsii to a threonine-containing medium resulted in a significant increase in the intracellular concentrations of L-threonine, glycine, serine and glyoxylate, and a decrease in oxalate. Incubation with 14C-labelled L-threonine resulted in an immediate output of 14CO2, and an accumulation of labelled glycine and serine in the mycelium. L-Threonine (10(-2)M) increased branching, favoured formation of sclerotia, and induced the formation of enzymes I to VIII, but not IX and X. Sodium oxalate (1-5 X 10(-2)M) inhibited branching, sclerotium formation and the activity of enzymes III and IV. Glycine (10(-1) M) inhibited branching, sclerotium formation and activity of I and II. Ammonium chloride (10(-1) to 10(-2) M) inhibited formation of sclerotia, threonine uptake and activity of III. Acetyl-CoA inhibited V and L-cysteine inhibited I as well as sclerotium formation and branching. It is suggested that hyphal morphogenesis and formation of sclerotia in S. rolfsii require an increased supply of carbohydrate intermediates and energy and that these are mainly supplied by the glyoxylate pathway.
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PMID:Metabolism of L-threonine and its relationship to sclerotium formation in Sclerotium rolfsii. 98 16

Treatment of rats with the vitamin B12 analogue hydroxy-cobalamin[c-lactam] (HCCL) impairs methylmalonyl-CoA mutase function and leads to methylmalonic aciduria due to intracellular accumulation of propionyl and methylmalonyl-CoA. Since accumulation of these acyl-CoAs disrupts normal cellular regulation, the present investigation characterized metabolism in hepatocytes and liver mitochondria from rats treated subcutaneously with HCCL or saline (control) by osmotic minipump. Consistent with decreased methylmalonyl-CoA mutase activity, 14CO2 production from 1-14C-propionate (1 mM) was decreased by 76% and 82% after 2-3 wk and 5-6 wk of HCCL treatment, respectively. In contrast, after 5-6 wk of HCCL treatment, 14CO2 production from 1-14C-pyruvate (10 mM) and 1-14C-palmitate (0.8 mM) were increased by 45% and 49%, respectively. In isolated liver mitochondria, state 3 oxidation rates were unchanged or decreased, and activities of the mitochondrial enzymes, citrate synthetase, succinate dehydrogenase, carnitine palmitoyltransferase, and glutamate dehydrogenase (expressed per milligram mitochondrial protein) were unaffected by HCCL treatment. In contrast, activities of the same enzymes were significantly increased in both liver homogenate (expressed per gram liver) and isolated hepatocytes (expressed per 10(6) cells) from HCCL-treated rats. The mitochondrial protein per gram liver, calculated on the basis of the recovery of the mitochondrial enzymes, increased by 39% in 5-6 wk HCCL-treated rats. Activities of lactate dehydrogenase, catalase, cyanide-insensitive palmitoyl-CoA oxidation, and arylsulfatase A in liver were not affected by HCCL treatment. Hepatic levels of mitochondrial mRNAs were elevated up to 10-fold in HCCL-treated animals as assessed by Northern blot analysis. Thus, HCCL treatment is associated with enhanced mitochondrial oxidative capacity and an increased mitochondrial protein content per gram liver. Increased mitochondrial oxidative capacity may be a compensatory mechanism in response to the metabolic insult induced by HCCL administration.
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PMID:Increased hepatic mitochondrial capacity in rats with hydroxy-cobalamin[c-lactam]-induced methylmalonic aciduria. 170 51

Hepatic dysfunction caused by oxidative stress when secondary peroxidation products were administered orally was investigated in rat. In serum at 24 hr after the administration of secondary products, the contents of lipid peroxides reached a maximum, the level of tocopherol reached a minimum, and the transaminase activities were elevated. In the liver, the lipid peroxide contents were kept high between 6 and 24 hr and tocopherol level was kept low between 15 and 48 hr after the does. Therefore, the hepatic oxidative stress was most severe around 15 hr after the dose. Dysfunction in the liver having oxidative stress was then made clear. One was a disturbance in synthetic system of glucose 6-phosphate. The decreases in activities of phosphoglucomutase and glucokinase reduced a level of glucose 6-phosphate, which suppressed the supply of NADPH in pentose cycle, while the NADPH was consuming well for detoxification of endogenous lipid peroxides. Another was specific inactivations of mitochondrial succinate dehydrogenase and aldehyde dehydrogenase. A third was the depletion of CoASH, which induced the decreases in activities of citrate cycle and lipogenesis. The other was a formation of lipofuscin. Even after the liver was recovering from the oxidative stress, the liver was getting hypertrophy and lipofuscin was accumulating. To make the cause of hepatic dysfunction clear, it was examined whether the incorporated secondary products in the liver could directly attack the enzymes or not. A reasonable amount of secondary products present in the liver was estimated, and then the amount of secondary products was added in hepatic subcellular organelles in vitro. It was found that mitochondrial NAD-dependent aldehyde dehydrogenase, glucokinase, and CoASH were directly attacked and inactivated by the incorporated secondary products in the liver. Thus, a part of dietary secondary products was incorporated into liver, and was not detoxified, but injured the enzymes and CoASH. Then it resulted in lipofuscin formation.
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PMID:Hepatotoxicity caused by dietary secondary products originating from lipid peroxidation. 183 11

A short-term training program involving 2 h of daily exercise at 59% of peak O2 uptake (VO2max) repeated for 10-12 consecutive days was employed to determine the significance of adaptations in energy metabolic potential on alterations in energy metabolism and substrate utilization in working muscle. The initial VO2max determined before training on the eight male subjects was 53.0 +/- 2.0 (SE) ml.kg-1.min-1. Analysis of samples obtained by needle biopsy from the vastus lateralis muscle before exercise (0 min) and at 15, 60, and 99 min of exercise indicated that on the average training resulted (P less than 0.05) in a 6.5% higher concentration of creatine phosphate, a 9.9% lower concentration of creatine, and a 39% lower concentration of lactate. Training had no effect on ATP concentration. These adaptations were also accompanied by a reduction in the utilization in glycogen such that by the end of exercise glycogen concentration was 47.1% higher in the trained muscle. Analysis of the maximal activities of representative enzymes of different metabolic pathways and segments indicated no change in potential in the citric acid cycle (succinate dehydrogenase, citrate synthase), beta-oxidation (3-hydroxyacyl CoA dehydrogenase), glucose phosphorylation (hexokinase), or potential for glycogenolysis (phosphorylase) and glycolysis (pyruvate kinase, phosphofructokinase, alpha-glycerophosphate dehydrogenase, lactate dehydrogenase). With the exception of increases in the capillary-to-fiber area ratio in type IIa fibers, no change was found in any fiber type (types I, IIa, and IIb) for area, number of capillaries, capillary-to-fiber area ratio, or oxidative potential with training.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early muscular and metabolic adaptations to prolonged exercise training in humans. 186 84

The effects of rotenone on the succinate-driven reduction of matrix nicotinamide nucleotides were investigated in Percoll-purified mitochondria from potato (Solanum tuberosum) tubers. Depending on the presence of ADP or ATP, rotenone caused an increase or a decrease in the level of reduction of the matrix nicotinamide nucleotides. The increase in the reduction induced by rotenone in the presence of ADP was linked to the oxidation of the malate resulting from the oxidation of succinate. Depending on the experimental conditions, malic enzyme (at pH 6.6 or in the presence of added CoA) or malate dehydrogenase (at pH 7.9) were involved in this oxidation. At pH 7.9, the oxaloacetate produced progressively inhibited the succinate dehydrogenase. In the presence of ATP the production of oxaloacetate was stopped, and succinate dehydrogenase was protected from inhibition by oxaloacetate. However, previously accumulated oxaloacetate transitorily decreased the level of the reduction of the NAD+ driven by succinate, by causing the reversal of the malate dehydrogenase reaction. Under these conditions (i.e. presence of ATP), rotenone strongly inhibited the reduction of NAD+ by succinate-driven reverse electron flow. No evidence for an active reverse electron transport through a rotenone-insensitive path could be obtained. The inhibitory effect of rotenone was masked if malate had previously accumulated, owing to the malate-oxidizing enzymes which reduced part or all of the matrix NAD+.
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PMID:Succinate-driven reverse electron transport in the respiratory chain of plant mitochondria. The effects of rotenone and adenylates in relation to malate and oxaloacetate metabolism. 200 Dec 41

Oxidation of [3-13C]propionate was studied in cultured yeast cells, and the distribution of label in the 2- and 3-positions of alanine was detected by 13C NMR. [3-13C]Propionate forms [2-13C]succinyl-CoA in the mitochondria which then enters the citric acid cycle and forms malate through two symmetrical intermediates, succinate and fumarate. If these symmetrical intermediates randomly diffuse from one enzyme to the next in mitochondria as is normally assumed, then 13C labeling in malate C2 and C3 must be equal. However, any direct transfer of metabolites from site to site between succinate thiokinase, succinate dehydrogenase, and fumarase would result in an uneven distribution of 13C in malate C2 and C3 and any molecules derived from malate. Since pyruvate may be derived from malate via the malic enzyme and subsequently converted into alanine by transamination, any 13C asymmetry in alanine C2 and C3 must directly reflect the 13C distribution in the malate pool. During oxidation of [3-13C]propionate, we detect a significant quantity of labeled alanine, where 13C enrichment in C3 is significantly higher than that in C2. Inhibition of succinate dehydrogenase with malonate or creating conditions that increase the chances of a back-reaction (from malate to fumarate) result in a significant decrease in the asymmetric labeling of alanine. Ubiquinone-deficient yeast cells (having only 10% of the oxidative capacity of wild-type cells) could slowly oxidize propionate, but in this case the 13C labeling was equal in the C2 and C3 of alanine, showing that isotope randomization had occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Channeling of TCA cycle intermediates in cultured Saccharomyces cerevisiae. 212 73

Recent studies in patients with long-term heart failure have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise. The present study provides an analysis of substrate and enzyme content, fiber typing, and capillarization in skeletal muscle biopsy samples obtained at rest from the vastus lateralis in 11 patients with long-term heart failure (left ventricular ejection fraction, 21 +/- 8%) and nine normal subjects. Patients demonstrated a reduced peak exercise oxygen consumption (13.0 +/- 3.3 ml/kg/min) when compared with normals (30.2 +/- 8.6 ml/kg/min, p less than 0.001) and had an accelerated rise in blood lactate levels during exercise. In mixed fiber skeletal muscle, total phosphorylase and glycolytic enzyme activities were not different in the two groups, whereas mitochondrial enzymes involved in terminal oxidation were decreased in patients as compared with normal subjects as indicated by reductions in succinate dehydrogenase (51 +/- 15 vs. 81 +/- 17 microM/g protein/min, p less than 0.001) and citrate synthetase (26 +/- 7 vs. 43 +/- 20 microM/g protein/min, p less than 0.05). 3-Hydroxyacyl-CoA-dehydrogenase, an important enzyme mediating beta-oxidation of fatty acids, was also reduced in patients as compared with normals (18 +/- 7 vs. 27 +/- 10 microM/g protein/min, p less than 0.05). There was no difference in high-energy phosphagens or lactate concentration of mixed muscle in the two groups, whereas glycogen content was decreased in patients (262 +/- 29 vs. 298 +/- 35 microM glucosyl units/kg dry wt, p = 0.01). Patients demonstrated a reduced percentage of slow twitch type I fibers (36 +/- 7% vs. 52 +/- 22%, p less than 0.05) and had a higher percentage of type IIb fast twitch fibers (24 +/- 9% vs. 11 +/- 12%, p = 0.02), which were smaller than the type IIb fibers seen in normal subjects (p less than 0.05). In patients, the number of capillaries per fiber was decreased for type I and type IIa fibers (both, p less than 0.03), but the ratio of capillaries to cross-sectional fiber area was not different for the two groups. These data demonstrate major alterations in skeletal muscle histology and biochemistry in patients with long-term heart failure, including fiber atrophy, a decrease in percentage of composition of type I fibers, and an increase in type IIb fibers accompanied by a decrease in oxidative enzyme capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure. 229 59


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