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

We have previously shown that citrate synthase binds to an intrinsic protein of the mitochondrial inner membrane (D'Souza and Srere, 1983). In this paper we present evidence that this citrate synthase binding protein is the citrate transporter. We have used citrate synthase 1 mutants of Saccharomyces cerevisiae and transformants containing citrate synthase inactivated by site-directed mutagenesis to study the effect of the CS1 protein upon mitochondrial function (Kispal and Srere). In the present study citrate uptake and oxidation were measured during state 3 conditions (presence of 200 microM ADP) in the mitochondria of several strains of Saccharomyces cerevesiae: a parental strain containing wild-type mitochondrial citrate synthase (CS1) and strains derived from a CS1 deficient strain in which the CS1 gene was disrupted by insertion of the LEU2 gene. These strains were generated from the CS1- cells by transformation with vectors encoding site-specific mutants of CS1 possessing very low levels of enzymatic activity. One such strain in this study was subsequently found to have undergone reversion to produce a strain which had activity very similar to wild type. Positive correlation between citrate uptake and the rate of citrate oxidation was found, suggesting coupling of the two processes. Both mitochondrial citrate uptake and oxidation were decreased in the mutant lacking any form of CS1 protein. Reintroduction of mutagenized CS1 into yeast causes an enhancement in the rate of state 3 oxygen consumption and of citrate uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Recognit
PMID:Citrate synthase 1 interacts with the citrate transporter of yeast mitochondria. 209 88

Previous studies have shown that dietary provision of carbohydrate can alter cardiac isomyosin distribution in hormonally deficient rats. The main objective of this study was to determine if varying the heart's potential to utilize carbohydrate for energy provision can influence the cardiac isomyosin expression in normal weanling rats. Animals were assigned to one of five groups according to dietary and/or metabolic treatment: (1) mixed-control--(M); (2) high carbohydrate--(H); (3) low carbohydrate--(L); (4) mixed-diet supplemented with oxfenicine, a cardiospecific fatty acid oxidation inhibitor--(MO); and (5) high carbohydrate diet supplemented with oxfenicine--(HO). The results show that 4 weeks of dietary manipulations aimed to either increase or decrease carbohydrate supply to the heart, failed to induce any alterations in either cardiac myosin ATPase activity or isoenzyme pattern. However, extremes in carbohydrate provision altered the metabolic properties of both heart and skeletal muscle. A low carbohydrate diet increased 3-hydroxyacyl CoA dehydrogenase (P less than 0.05) and citrate synthase activities (P less than 0.05) and decreased glycogen content in both heart and soleus muscle; whereas, a high carbohydrate diet, in conjunction with oxfenicine, tended to increase hexokinase activity in these same tissues. These alterations provide indirect evidence that the contributions of both fat and carbohydrate to the energy balance of the heart and skeletal muscle were altered by the imposed dietary interventions. Collectively, these results suggest that although the substrate utilization patterns of the normal weanling heart can be modified via dietary manipulation, such shifts do not exert any regulatory influence on cardiac isomyosin expression.
J Mol Cell Cardiol 1990 Mar
PMID:Dietary effects on cardiac metabolic properties in rodents. 214 63

The product of the CIT2 gene has the tripeptide SKL at its carboxyl terminus. This amino acid sequence has been shown to act as a peroxisomal targeting signal in mammalian cells. We examined the subcellular site of this extramitochondrial citrate synthase. Cells of Saccharomyces cerevisiae were grown on oleate medium to induce peroxisome proliferation. A fraction containing membrane-enclosed vesicles and organelles was analyzed by sedimentation on density gradients. In wild-type cells, the major peak of citrate synthase activity was recovered in the mitochondrial fraction, but a second peak of activity cosedimented with peroxisomes. The peroxisomal activity, but not the mitochondrial activity, was inhibited by incubation at pH 8.1, a characteristic of the extramitochondrial citrate synthase encoded by the CIT2 gene. In a strain in which the CIT1 gene encoding mitochondrial citrate synthase had been disrupted, the major peak of citrate synthase activity was peroxisomal, and all of the activity was sensitive to incubation at pH 8.1. Yeast cells bearing a cit2 disruption were unable to mobilize stored lipids and did not form stable peroxisomes in oleate. We conclude that citrate synthase encoded by CIT2 is peroxisomal and participates in the glyoxylate cycle.
Mol Cell Biol 1990 Apr
PMID:Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae is peroxisomal. 218 Dec 73

We isolated a cDNA clone from Arabidopsis thaliana encoding the TCA cycle enzyme, citrate synthase. The plant enzyme displays 48% and 44% amino acid residue similarity with the pig, and yeast polypeptides, respectively. Many proteins, including citrate synthase, which are destined to reside in organelles such as mitochondria and chloroplasts, are the products of the nucleocytoplasmic protein synthesizing machinery and are imported post-translationally to the site of function. We present preliminary investigations toward the establishment of an in vitro plant mitochondrial import system allowing for future studies to dissect this process in plants where the cell must differentiate between mitochondria and chloroplast and direct their polypeptides appropriately.
Plant Mol Biol 1989 Oct
PMID:Isolation of a cDNA encoding mitochondrial citrate synthase from Arabidopsis thaliana. 249 64

The in vitro metabolism of [1-13C]glucose by Ascaris suum third and fourth-stage larvae was analyzed under different gas phases using 13C nuclear magnetic resonance spectroscopy (13C-NMR). Third-stage larvae (L3) incubated under a gas phase of 85% N2/5% O2/10% CO2 produced trace amounts of [13C]succinate, and molted to fourth-stage larvae (L4) between days 3 and 4 in vitro. However, they appeared to arrest as L3s when incubated under air, or 85% N2/5% O2/10% CO2 in the presence of 2 mM potassium cyanide, or 95% N2/5% CO2. Day 12 L4 (eight days after molting) incubated under 85% N2/5% O2/10% CO2, or 95% N2/5% CO2, or 94% N2/1% O2/5% CO2, produced succinate, acetate, propionate and the branched-chain fatty acids 2-methylvalerate and 2-methylbutyrate by fermentative pathways characteristic of adult body wall muscle. In contrast, when Day 12 L4 were incubated under air, only trace amounts of these acids were detected in the incubation medium. Thus, L4 are capable of synthesizing end-products typical of the adult even in the presence of oxygen, as long as the CO2 tensions are above 5%. As would be predicted, activities of enzymes involved in aerobic metabolism, including citrate synthase, isocitrate dehydrogenase, and cytochrome oxidase, decreased dramatically as L4s underwent the final ecdysis and matured to the adult stage. More importantly, activities of enzymes typical of anaerobic metabolism, including phosphoenolpyruvate carboxykinase and malic enzyme, were substantially elevated in L3s (over their levels in second-stage larvae), and appeared to have reached their adult levels in L3s prior to the third molt, even though L3s still exhibited cyanide sensitivity. Since L3s and L4s have enzymes involved in both aerobic and anaerobic pathways, it is possible that the L3s contain two populations of mitochondria, one which functions aerobically and a second which functions anaerobically.
Mol Biochem Parasitol 1989 Aug
PMID:Effect of gas phase on carbohydrate metabolism in Ascaris suum larvae. 250 8

The effect of Ca2+-homopantothenate (HOPA) treatment (250 mg/kg for 5 d) has been studied by evaluating the specific activity of enzymes related to: glycolytic pathway (hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase), tricarboxylic acid cycle (citrate synthase, malate dehydrogenase), mitochondrial electron transfer chain (succinate dehydrogenase, cytochrome oxidase), NADH redox state (NADH cytochrome c reductase), acetylcholine metabolism (acetylcholinesterase), and glutamate metabolism (glutamate dehydrogenase). The enzymatic activity assays were performed on homogenate in toto, nonsynaptic mitochondria and synaptosomes isolated from: cerebral cortex, hippocampus, striatum, hypothalamus, medulla oblongata, and cerebellum of normoxic rats and rats submitted to intermittent normobaric hypoxia (90:10, N2:O2). In normoxic rats, HOPA was unable to induce any modification. Hypoxia per se induced a decrease in the activity of synaptosomal cytochrome oxidase in cerebral cortex, hippocampus, and cerebellum.
Mol Chem Neuropathol 1989 Jun
PMID:Effect of Ca2+-homopantothenate and mild hypoxia on some enzyme activities evaluated in subcellular fractions from different rat brain regions. 254 16

In-vitro translation of anglerfish islet mRNA revealed three glucagon precursors (preproglucagons): one with Mr 16,000 and two with Mr 14,000. The two Mr 14,000 precursors were well separated upon isoelectric focusing gels (pI values of 7.2 and 7.3), but had identical peptide maps. Translation of hybrid-selected Mr 14,000 preproglucagon mRNA in the presence of microsomal vesicles revealed that both precursors were processed to the same proglucagon. Northern blot analysis detected two mRNA species encoding Mr 14,000 precursor. A full-length Mr 14,000 preproglucagon cDNA was subcloned into a transcription vector, and coupled in-vitro transcription-translation was performed; surprisingly, both Mr 14,000 precursors were synthesized. To test whether acetylation of the free amino terminus generated the more acidic precursor, acetylase activity was partially inactivated with the inhibitor S-acetonyl-CoA, and acetyl-CoA was depleted by addition of oxaloacetate and citrate synthetase. Under these conditions, the level of the most basic preproglucagon was greatly enhanced, but when exogenous acetyl-CoA was added, the acidic form predominated. We conclude that acetylation generates the acidic precursor, and we discuss the implications of our findings for the biogenesis of other peptide hormones.
J Mol Endocrinol 1989 Mar
PMID:In-vitro biosynthesis of multiple preproglucagons results from acetylation of the primary translation products. 267 84

Selected biochemical parameters of the ventricular myocardium were compared among several orders of adult mammals with established differences in resting heart rate (cattle, 51 beats/min; swine, 68; canine, 107; rabbit, 256; guinea-pig, 273; rat, 355; mouse, 475). It was hypothesized that the biochemical character of mammalian myocardia is associated with the chronic functional demand on the muscle. Therefore, differences observed in the myocardial biochemical potential among the species could reflect differences in resting heart rate. Myocardia from smaller mammals with higher resting heart rate had significantly (P less than 0.05) higher maximal activities of citrate synthase, 3-hydroxyacyl-CoA dehydrogenase, lactate dehydrogenase (muscle/total), hexokinase and oxidation rates of glucose and palmitate than did larger mammals with lower resting heart rate. Maximal activities of phosphorylase and phosphofructokinase were more uniform across the animals. Correlation coefficients determined among average values of measured biochemical parameters and resting heart rate indicated that resting heart rate was closely associated with: citrate synthase (r = 0.86), 3-hydroxyacyl-CoA dehydrogenase (r = 0.93), ratio muscle/total lactate dehydrogenase (r = 0.89), hexokinase (r = 0.89), glucose oxidation (r = 0.88), and palmitate oxidation (r = 0.93). Significant correlations were observed among all of these parameters with the exception of citrate synthase vs. 3-hydroxyacyl-CoA dehydrogenase, and glucose oxidation vs. muscle/total lactate dehydrogenase. It was concluded that the oxidative capacity of mammalian myocardia was closely associated with resting heart rate, whereas the glycolytic potential of the myocardia was more uniform among the species.
J Mol Cell Cardiol 1989 Apr
PMID:Biochemical characteristics of mammalian myocardia. 274 58

A method for a 50-60-fold purification of a cysteine proteinase from trophozoites of Entamoeba histolytica using 35-80% ammonium sulphate fractionation, gel chromatography on Sephadex G-75, and preparative isoelectric focusing is described. The enzyme was examined for its proteolytic potencies towards native enzyme substrates. The amebic proteinase directly inactivates aldolase and glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle as well as glucose-6-phosphate dehydrogenase from yeast. The inactivation of citrate synthase from porcine heart proceeds rather slowly, whereas malate dehydrogenase from porcine heart is not affected by the amebic proteinase under the condition used. With the exception of aldolase all inactivated enzyme substrates have been cleaved by limited proteolyses yielding major cleavage products. The inactivation of aldolase probably functions by the release of a small segment from a terminus being essential for aldolase activity.
Mol Biochem Parasitol 1986 Jan
PMID:Cysteine proteinase of Entamoeba histolytica. I. Partial purification and action on different enzymes. 287 Apr 30

The purpose of this study was to determine whether thyroid hormone could directly affect the phenotypic expression of two isozymic systems [lactate dehydrogenase (LDH) and myosin] and the energy transducing potential of cultured neonatal heart cells. In addition we determined if these biochemical systems developed in culture as they normally do during in vivo post-natal development. Cells were maintained for 14 days in culture medium containing 10% horse serum and Earle's salts. Experimental cultures were supplemented with 10 nmol/l 3,3',5-triiodo-L-thyronine (T3). Hearts used to study in vivo development were excised from rats at the ages of 2 and 14 days post-natal to correspond with the time of isolating and harvesting the cultured heart cells, respectively. Adult hearts were used to represent the final developmental stage. Cultured cardiomyocytes without T3 administered to the culture medium showed no change in the isozymic profiles (myosin and LDH) or in metabolic potential during the 2 week culture period. The T3 treated cultures showed a complete shift to the V1 myosin isozyme. The glycolytic and aerobic metabolic potential [i.e., phosphofructokinase (PFK) and citrate synthase (CS) activities] and the LDH isozyme distribution were unaltered by T3 treatment. During in vivo development a shift toward the V1 myosin and H-LDH isozymes along with an increase in aerobic metabolism occurred in the rat heart. These findings indicate that the development of these selected biochemical systems in cultured cardiac myocytes does not result from an intrinsic myogenetic program and thus must be regulated in vivo by epigenetic factor(s). These results show that T3 has the potential to be the prime determinant of the phenotypic expression of the myosin isoforms, but does not have the potential to be the sole determinant for the expression of the LDH isozymes or the glycolytic (PFK) and aerobic (CS) capacities of cardiac muscle cells.
J Mol Cell Cardiol 1988 Aug
PMID:The effects of triiodothyronine on cultured neonatal rat cardiac myocytes. 297 10


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