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

---

Query: EC:2.3.3.1 (citrate synthase)
4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Citrate synthase catalyses the initial reaction of the citric acid cycle and can therefore be considered as the rate-controlling enzyme for the entry of substrates into the cycle. In Corynebacterium glutamicum, the specific activity of citrate synthase was found to be independent of the growth substrate and of the growth phase. The enzyme was not affected by NADH or 2-oxoglutarate and was only weakly inhibited by ATP (apparent Ki = 10 mM). These results suggest that in C. glutamicum neither the formation nor the activity of citrate synthase is subject to significant regulation. The citrate synthase gene, gltA, was isolated, subcloned on plasmid pJC1 and introduced into C. glutamicum. Relative to the wild-type the recombinant strains showed six- to eightfold higher specific citrate synthase activity. The nucleotide sequence of a 3007 bp DNA fragment containing the gltA gene and its flanking regions was determined. The predicted gltA gene product consists of 437 amino acids (M(r) 48,936) and shows up to 49.7% identity with citrate synthase polypeptides from other organisms. Inactivation of the chromosomal gltA gene by gene-directed mutagenesis led to absence of detectable citrate synthase activity and to citrate (or glutamate) auxotrophy, indicating that only one citrate synthase is present in C. glutamicum. Transcriptional analysis by Northern (RNA) hybridization and primer extension experiments revealed that the gltA gene is monocistronic (1.45 kb mRNA) and that its transcription initiates at two consecutive G residues located 121 and 120 bp upstream of the translational start.
...
PMID:Nucleotide sequence, expression and transcriptional analysis of the Corynebacterium glutamicum gltA gene encoding citrate synthase. 752 44

The case of a female patient with cardio-encephalo-myopathy who died of her illness at one year of age, similarly to her three sisters, is reported. In autopsy samples, like muscle, heart, liver and cerebellum activities of several mitochondrial enzymes were determined. In the skeletal muscle serious decrease of carnitine acetyltransferase was observed (from the normal 4.8 U/g to 0.08 U/g wet weight), while in other tissues this activity was normal. In the muscle activities of several other mitochondrial enzymes were also decreased (cytochrome oxidase, NADH cytochrome C oxidoreductase, citrate synthase), while in other tissues there were no similar changes. Serious distortion was observed in the structure of the majority of mitochondria of muscle and heart by electronmicroscopy. The number of the Purkinje-cells in the cerebellum decreased, and the cells were shrunken, their axons were fragmented and disoriented. Also the structure of the mitochondria was abnormal in the Purkinje-cells, while it was normal in other areas of the cerebrum. In te tissues of the patient normal and deleted mitochondrial DNA coexisted as which could explain the genetic background of this disease at molecular level.
...
PMID:[Mitochondrial DNA deletion in hereditary cardio-encephalo-myopathy]. 759 86

We investigated how NADH generated during peroxisomal beta-oxidation is reoxidized to NAD+ and how the end product of beta-oxidation, acetyl-CoA, is transported from peroxisomes to mitochondria in Saccharomyces cerevisiae. Disruption of the peroxisomal malate dehydrogenase 3 gene (MDH3) resulted in impaired beta-oxidation capacity as measured in intact cells, whereas beta-oxidation was perfectly normal in cell lysates. In addition, mdh3-disrupted cells were unable to grow on oleate whereas growth on other non-fermentable carbon sources was normal, suggesting that MDH3 is involved in the reoxidation of NADH generated during fatty acid beta-oxidation rather than functioning as part of the glyoxylate cycle. To study the transport of acetyl units from peroxisomes, we disrupted the peroxisomal citrate synthase gene (CIT2). The lack of phenotype of the cit2 mutant indicated the presence of an alternative pathway for transport of acetyl units, formed by the carnitine acetyltransferase protein (YCAT). Disruption of both the CIT2 and YCAT gene blocked the beta-oxidation in intact cells, but not in lysates. Our data strongly suggest that the peroxisomal membrane is impermeable to NAD(H) and acetyl-CoA in vivo, and predict the existence of metabolite carriers in the peroxisomal membrane to shuttle metabolites from peroxisomes to cytoplasm and vice versa.
...
PMID:The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions. 762 49

Muscle cell fiber types in gracilis, rectus femoris, and long head of triceps brachii muscles of ferrets and dogs were identified on serial sections stained for myosin ATPase after preincubation at pH values of 9.8, 4.6, and 4.3 and for NADH-tetrazolium reductase (NADH-TR) activity. Although fiber types I and II were identified, the ATPase stain did not demonstrate classic type IIA/IIB fiber differences in either species. However, two type II fiber subtypes could be distinguished in the ferret because they differed slightly in staining intensity with ATPase at pH 4.3 and markedly with NADH-TR. One ferret type II fiber (designated II dark or IID) was smaller, slightly darker on ATPase, more oxidative on NADH-TR, and comprised more muscle volume than the other type II fiber (designated II light IIL). The IID fibers of ferret may represent the IID/X fibers of other authors. Both ferret type II fiber subtypes stained darker at pH 4.3 than canine II fibers. The NADH-TR staining indicated high oxidative activity in canine and ferret type I fibers. In contrast, type II fibers in the dog and IIL fibers in the ferret were moderately oxidative. Canine type IIC fibers were intermediate between type I and type II, whereas in the ferret, type IIC fibers were highly oxidative, as were type IID fibers. Ferret muscles are more oxidative than canine muscles according to NADH-TR staining. Also, ferret muscles possess 40-100% higher citrate synthase activity as compared to canine muscles.
...
PMID:Comparison of muscle cell fiber types and oxidative capacity in gracilis, rectus femoris, and triceps brachii muscles in the ferret (Mustela putorius furo) and the domestic dog (Canis familiaris). 769 Oct 36

The energy metabolism was evaluated in gastrocnemius muscle from 3-month-old rats subjected to either mild or severe 4-week intermittent normobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, alpha-adrenergic (delta-yohimbine), vasodilator (papaverine, pinacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Furthermore the Vmax of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The adaptation to chronic intermittent normobaric mild or severe hypoxia induced alterations of the components in the anaerobic glycolytic pathway [as supported by the increased activity of lactate dehydrogenase and/or hexokinase, resulting in the decreased glycolytic substrate concentration consistent with the increased lactate production and lactate-to-pyruvate ratio] and in the mitochondrial mechanism [as supported by the decreased activity of malate dehydrogenase and/or citrate synthase resulting in the decreased concentration of some key components in the tricarboxylic acid cycle]. The effect of the concomitant pharmacological treatment suggests that the action of CNS-acting drugs could be also related to their direct influence on the muscular biochemical mechanisms linked to energy transduction.
...
PMID:Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism. 778 38

The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.
...
PMID:Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and TRH-analogue treatment. 781 45

We have purified the citrate synthase from Azotobacter vinelandii and have determined that the size of the subunit is 48,000 Da and the structure of the holoenzyme is a hexamer. This contrasts with earlier estimates that indicate a 58,000 Da subunit and a tetrameric structure. In addition, the enzyme is allosteric with a Hill coefficient of 1.5 and is inhibited by NADH. The Hill coefficient is changed to about 1 by high ionic strength and AMP. The enzyme is thus similar to the citrate synthases of many other Gram-negative, facultative, anaerobic organisms. In addition, the amino acid sequence of about 100 residues has been determined and found to be highly similar to the sequence of Pseudomonas aeruginosa citrate synthase.
...
PMID:Azotobacter vinelandii citrate synthase. 781 5

Previous studies demonstrated that one of the most significant cellular responses of the rabbit urinary bladder to partial outlet obstruction is a 50% decrease in the activities of the mitochondrial enzymes citrate synthase and malate dehydrogenase, when calculated as either activity per unit mass or activity per mg protein. A major question arose from these studies: Are the mitochondrial enzyme activities per mitochondrion reduced, or is the number of mitochondria per unit tissue mass reduced? The current experiments were designed to study the sequential changes in the activities of mitochondrial oxidative enzymes following partial outlet obstruction. The activities of NADH-cytochrome c reductase (NCCR), cytochrome oxidase (CO), citrate synthase (CS) and malate dehydrogenase (MDH) were measured in whole tissue homogenates and in mitochondrial preparations of separated bladder mucosa and muscle, from normal bladders, and, from hypertrophied bladders at 1, 3, and 7 days following partial outlet obstruction. The results can be summarized as follows: 1) Whole tissue homogenates: Activities of all enzymes were reduced to approximately 50% of control at 1 day following partial outlet obstruction. NCCR and CO activities returned to 75 and 85% of control respectively by 7 days post-obstruction; CS activity did not show any significant recovery over the 7 day period. 2) Mucosal and smooth muscle mitochondrial preparations: Activities of all enzymes were decreased significantly by 50% or greater at 1 day following partial outlet obstruction. The cytochrome (NCCR and CO) enzyme activities returned to control levels by 7 days post-obstruction; CS activity showed only a minor recovery over this time period. These results show that mitochondrial enzyme activity is significantly impaired immediately following partial outlet outlet obstruction, and whereas the activity of the cytochrome enzymes NCCR and CO recover to control levels (in the mitochondrial preparations) within 7 days post obstruction, the Krebs cycle enzymes (CS and MD) show no significant recovery. Thus, the regulatory mechanisms for the cytochromes is significantly different from that for the enzymes of the krebs cycle.
...
PMID:Alterations of mitochondrial oxidative metabolism in rabbit urinary bladder after partial outlet obstruction. 787 5

Non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities, NADH-cytochrome c reductase rotenone insensitive (marker of the outer membrane) and cytochrome oxidase (marker of the inner membrane), were measured in rat brain hippocampus and striatum immediately after and 1, 4 and 7 days following the induction of complete transient ischemia (15 min) by the four vessel occlusion method. Furthermore citrate synthetase activity was measured with and without Triton X-100 in order to qualitatively evaluate the membrane permeability. Non-synaptosomal mitochondrial membranes showed reduction of both activities only in the late reperfusion phase: NADH-CCRRi decreased in striatal mitochondria after 4-7 days and only after 7 days in the hippocampus. COX activity decreased only in striatal mitochondria 7 days after ischemia. Non-synaptosomal mitochondrial membrane permeability did not show changes. Synaptosomal mitochondria showed a decrease of NADH-CCRRi only at 7 days of reperfusion both in hippocampus and striatum, while COX activity decreased only during ischemia and returned to normal levels in the following days in the two areas considered. In summary, free mitochondria showed insensitiveness to ischemia but they resulted damaged in the late reperfusion phase, while mitochondria from the synaptic terminal showed ischemic damage, partially restored during reperfusion. The striatal mitochondria showed a major susceptibility to ischemia/reperfusion damage, showing changes earlier than the hippocampal ones.
...
PMID:Changes in non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities after transient cerebral ischemia. 787 28

To study the distribution of oxidative capacity in muscle fibers, mitochondrial volume density and the oxidative capacity of isolated mitochondria were evaluated. Mitochondria were isolated from the subsarcolemmal and interfibrillar areas of the soleus (a muscle largely made up of slow oxidative fibers) and the gastrocnemius medial head (a muscle largely made up of fast glycolytic fibers) of the rat, and their oxidative capacities were evaluated using NADH- and FADH-generating substrates. In the soleus muscle, the subsarcolemmal mitochondria showed a lower oxidative capacity than interfibrillar mitochondria when NADH-generating substrates were used. This difference was not observed when FADH-generating substrates were used. In the gastrocnemius, there were no differences in the oxidative capacity of the subsarcolemmal and the interfibrillar mitochondria. Additionally, citrate synthase activity was found to be lower in mitochondria isolated from the subsarcolemmal area of the soleus than in the other mitochondrial preparations. These findings indicate that the difference in oxidative capacity of the isolated mitochondria is not related to differences in the inner mitochondrial membranes. Mitochondrial volume density was evaluated using electron micrographs of the subsarcolemmal and interfibrillar areas of slow oxidative fibers from the soleus and fast glycolytic fibers from the gastrocnemius. In the slow oxidative fibers, mitochondrial volume density in the subsarcolemmal area was four times higher than in the interfibrillar area. In the fast glycolytic fibers, mitochondrial volume densities in the subsarcolemmal and interfibrillar areas did not differ from that of the interfibrillar area of the slow oxidative fibers. The oxidative capacity of the tissue, calculated by multiplying the mitochondrial oxidative capacities by the mitochondrial volume densities, was 2-4 times higher in the subsarcolemmal areas of the soleus fibers than in the other areas studied. This was true in spite of the fact that the oxidative capacity of the subsarcolemmal mitochondria of the slow oxidative fibers was lower than those of the other mitochondrial populations studied. These results indicate that the difference in oxidative capacity between slow oxidative fibers and fast glycolytic fibers is the result of the much greater mitochondrial volume density in the subsarcolemmal area of the slow oxidative fibers.
...
PMID:Oxidative capacity distribution in skeletal muscle fibers of the rat. 796 83


<< Previous 1 2 3 4 5 6 7 8 9 10

---