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)

Rao, G. Ramananda (Indian Institute of Science, Bangalore, India), M. Sirsi, and T. Ramakrishnan. Enzymes in Candida albicans. II. Tricarboxylic acid cycle and related enzymes. J. Bacteriol. 84:778-783. 1962.-Evidence is presented to show the operation of the tricarboxylic acid cycle in Candida albicans, by studies with whole cells, cell-free preparations, and by the demonstration of most of the enzymes involved in the cycle. Cell-free extracts contained the following enzymes: condensing enzyme; aconitase; isocitric, alpha-ketoglutaric, succinic, and malic dehydrogenases; malic enzyme; fumarase; reduced diphosphopyridine nucleotide (DPNH) oxidase; DPNH-cytochrome c reductase; reduced triphosphopyridine nucleotide (TPNH) cytochrome c reductase; and diaphorase. Pyruvic dehydrogenase, TPNH oxidase, and transhydrogenase activities could not be detected under the test conditions.
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PMID:Enzymes in Candida albicans. II. Tricarboxylic acid cycle and related enzymes. 1397 46

Cooper, Robert C. (Michigan State University, East Lansing). Evidence for the presence of certain tricarboxylic acid cycle enzymes in Thiobacillus thioparus. J. Bacteriol. 88:624-629. 1964.-Various tricarboxylic acid cycle enzymes appear to be present in Thiobacillus thioparus. Cell-free extracts of T. thioparus were active for a number of tricarboxylic acid cycle enzymes, including aconitase, isocitric dehydrogenase, and malic dehydrogenase. Tests for the presence of fumarase and the condensing enzyme, citrogenase, were inconclusive. Citrate was shown to be active in the metabolism of T. thioparus, but the actual mechanism involved in its formation was not clear. The enzyme, isocitratase, appeared to be absent. Evidence for the presence of succinic dehydrogenase was found in experiments with whole cells. From these results, it would appear that T. thioparus has a terminal respiration pathway similar to that found in many heterotrophic microorganisms.
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PMID:EVIDENCE FOR THE PRESENCE OF CERTAIN TRICARBOXYLIC ACID CYCLE ENZYMES IN THIOBACILLUS THIOPARUS. 1420 98

VanDemark, P. J. (Cornell University, Ithaca, N.Y.), and P. F. Smith. Evidence for a tricarboxylic acid cycle in Mycoplasma hominis. J. Bacteriol. 88:1602-1607. 1964.-Resting cells of acetate-grown Mycoplasma hominis strain 07 oxidized the various intermediates of the tricarboxylic and glyoxylate cycles, with the exception of sodium citrate and glyoxylate. Extracts of these cells possessed isocitric dehydrogenase, isocitratase, alpha-ketoglutaric dehydrogenase, succinic dehydrogenase, fumarase, malic dehydrogenase, citratase, and acetyl coenzyme A kinase activities. With the assay conditions employed, condensing enzyme, malate synthetase, and phosphotransacetylase activities were negligible. Incubation of sodium acetate-2-C(14) with the various intermediates of the tricarboxylic acid cycle in the presence of cell-free extracts resulted in exchange of the isotope with these compounds as well as the formation of other labeled intermediates of the tricarboxylic acid cycle. Oxidation of sodium acetate-2-C(14) alone resulted in the formation of labeled succinate, fumarate, and malate.
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PMID:EVIDENCE FOR A TRICARBOXYLIC ACID CYCLE IN MYCOPLASMA HOMINIS. 1424 Sep 45

Candida magnoliae which has been newly isolated from honey comb is an osmotolerant yeast to produce erythritol as a major product. Erythritol is a noncariogenic, low calorie sweetener and safe for diabetics. Strain development by chemical mutation to obtain the improved erythritol yield and productivity relative to the parental strain made it necessary to elucidate the physiological differences between the wild and mutant strains. Proteomic analyses of C. magnoliae wild and mutant strains with two-dimensional gel electrophoresis and nanoelectrospray mass spectrometry were carried out to identify intracellular proteins and to estimate the effects of newly characterized metabolic enzymes on the yeast cell growth and erythritol production. Most of the molecular mass of intracellular proteins were distributed in the range of pI 4-8 and molecular mass of approximately 130 kDa. Six out of nine protein spots expressed at different levels between the wild and mutant strains were analyzed with nanoelectrospray tandem mass spectrometry and identified by comparing amino acid sequences with the National Center for Biotechnology Information and Saccharomyces Genome Databases. Except for Ygr086cp, these proteins were believed to be the metabolic enzymes involved in the citric acid cycle (citrate synthase, succinyl-CoA ligase and fumarase) and the glycolysis pathway (pyruvate decarboxylase and enolase). Up-regulated enzymes in the citric acid cycle could explain high growth of the C. magnoliae mutant strain owing to the increased NADH and ATP formation. Down-regulated enolase and up-regulated fumarase in the mutant strain seemed to play a role in the improved bioconversion of erythrose-4-phosphate to erythritol compared with the wild strain.
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PMID:Proteomic analysis of Candida magnoliae strains by two-dimensional gel electrophoresis and mass spectrometry. 1467 84

The degradation of Aluminum-citrate by Pseudomonas fluorescens necessitated a major restructuring of the various enzymatic activities involved in the TCA and glyoxylate cycles. While a six-fold increase in fumarase (FUM EC 4.2.1.2) activity was observed in cells subjected to Al-citrate compared to control cells, citrate synthase (CS EC 4.1.3.7) activity experienced a two-fold increase. On the other hand, in the Al-stressed cells malate synthase (MS EC 4.1.3.2) activity underwent a five-fold decrease in activity. This modulation of enzymatic activities appeared to be evoked by Al stress, as the incubation of Al-stressed cells in control media led to the complete reversal of these enzymatic profiles. These observations were further confirmed by 1H NMR and 13C NMR spectroscopy. No significant variations were observed in the activities of other glyoxylate and TCA cycle enzymes, like isocitrate lyase (ICL EC 4.1.3.1), malate dehydrogenase (MDH EC 1.1.1.37), and succinate dehydrogenase (SDH EC 1.3.99.1). This reconfiguration of the metabolic pathway appears to favour the production of a citrate-rich aluminophore that is involved in the sequestration of Al.
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PMID:Adaptation of Pseudomonas fluorescens to Al-citrate: involvement of tricarboxylic acid and glyoxylate cycle enzymes and the influence of phosphate. 1475 38

Krebs cycle enzyme activities and levels of five metabolites were determined from livers of old mice (30 months) maintained either on control or on long-term caloric restriction (CR) diets (28 months). In CR mice, the cycle was divided into two major blocks, the first containing citrate synthase, aconitase and NAD-dependent isocitrate dehydrogenase which showed decreased activities, while the second block, containing the remaining enzymes, displayed increased activity (except for fumarase, which was unchanged). CR also resulted in decreased levels of citrate, glutamate and alpha-ketoglutarate, increased levels of malate, and unchanged levels of aspartate. The alpha-ketoglutarate/glutamate and malate/alpha-ketoglutarate ratios were higher in CR, in parallel with previously reported increases with CR in pyruvate carboxylase activity and glucagon levels, respectively. The results indicate that long-term CR induces a differential regulation of Krebs cycle in old mice and this regulation may be the result of changes in gene expression levels, as well as a complex interplay between enzymes, hormones and other effectors. Truncation of Krebs cycle by CR may be an important adaptation to utilize available substrates for the gluconeogenesis necessary to sustain glycolytic tissues, such as brain.
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PMID:Krebs cycle enzymes from livers of old mice are differentially regulated by caloric restriction. 1528 89

We investigated whether substrate availability influences the type of energy metabolism in procyclic Trypanosoma brucei. We show that absence of glycolytic substrates (glucose and glycerol) does not induce a shift from a fermentative metabolism to complete oxidation of substrates. We also show that glucose (and even glycolysis) is not essential for normal functioning and proliferation of pleomorphic procyclic T. brucei cells. Furthermore, absence of glucose did not result in increased degradation of amino acids. Variations in availability of glucose and glycerol did result, however, in adaptations in metabolism in such a way that the glycosome was always in redox balance. We argue that it is likely that, in procyclic cells, phosphoglycerate kinase is located not only in the cytosol, but also inside glycosomes, as otherwise an ATP deficit would occur in this organelle. We demonstrate that procyclic T. brucei uses parts of the Krebs cycle for purposes other than complete degradation of mitochondrial substrates. We suggest that citrate synthase plus pyruvate dehydrogenase and malate dehydrogenase are used to transport acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, a process we show to occur in proliferating procyclic cells. The part of the Krebs cycle consisting of alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase was used for the degradation of proline and glutamate to succinate. We also demonstrate that the subsequent enzymes of the Krebs cycle, succinate dehydrogenase and fumarase, are most likely used for conversion of succinate into malate, which can then be used in gluconeogenesis.
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PMID:New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle. 1564 63

Mycobacterium tuberculosis (Mtb) has adapted its metabolism for persistence in the human macrophage. The adaptations are likely to involve Mtb's core intermediary metabolism, whose enzymes have been little studied. The tricarboxylic acid cycle is expected to yield precursors for energy, lipids, amino acids, and heme. The genome sequence of Mtb H37Rv predicts the presence of a complete tricarboxylic acid cycle, but we recently found that alpha-ketoglutarate dehydrogenase (KDH) activity is lacking in Mtb lysates. Here we showed that citrate synthase, aconitase, isocitrate dehydrogenase, fumarase, malate dehydrogenase, and succinate dehydrogenase, but not KDH, are present, raising the possibility of separate oxidative and reductive half-cycles. As a potential link between the half-cycles, we found that Rv1248c, annotated as encoding SucA, the putative E1 component of KDH, instead encodes alpha-ketoglutarate decarboxylase (Kgd) and produces succinic semialdehyde. Succinic semialdehyde dehydrogenase activity was detected in Mtb lysates and recapitulated with recombinant proteins GabD1 (encoded by Rv0234c) and GabD2 (encoded by Rv1731). Kgd and GabD1 or GabD2 form an alternative pathway from alpha-ketoglutarate to succinate. Rv1248c, which is essential or required for normal growth of Mtb [Sassetti, C., Boyd, D. H. & Rubin, E. J. (2003) Mol. Microbiol 48, 77-84] is the first gene shown to encode a Kgd. Kgd is lacking in humans and may represent a potential target for chemotherapy of tuberculosis.
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PMID:Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: identification of alpha-ketoglutarate decarboxylase. 1602 71

The activities of the citric acid cycle enzymes were determined in mitochondria isolated from kidneys of relatively young, middle age, and old mice. Aconitase exhibited the most significant decrease in activity with age. The activity of alpha-ketoglutarate dehydrogenase exhibited a modest decrease in activity, while NADP(+)-isocitrate dehydrogenase (NADP(+)-ICD) activity increased moderately with age. Activities of citrate synthase, NAD(+)-isocitrate dehydrogenase (NAD(+)-ICD), succinyl-CoA synthetase (SCS), succinate dehydrogenase (SD), fumarase (FUM), and malate dehydrogenase (MD) were not affected. The molar ratio of the intra-mitochondrial redox indicator, NADPH:NADP(+), was higher in young compared to old animals, while the NADH:NAD(+) molar ratio remained unchanged. It is suggested that an age-related decrease in aconitase activity along with relatively subtle alterations in activities of some other citric acid cycle enzymes are likely to contribute to a decline in the overall efficiency of mitochondrial bioenergetics. The biological consequences of such alterations include age-related fluctuations in the citric acid cycle intermediates, which are precursors of protein synthesis, activators of fatty acid synthesis, and can also act as ligands for orphan G-protein coupled receptors.
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PMID:Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice. 1628 53

Electron micrographs are presented which establish the identity of the components of the 3 major bands observed after sucrose density centrifugation of the crude particulate fraction from the endosperm of germinating castor bean seedlings. These are: mitochondria (density 1.19 g/cc), proplastids (density 1.23 g/cc) and glyoxysomes (density 1.25 g/cc). Further evidence is provided on the enzymatic composition of the glyoxysomes. Essentially all of the particulate malate synthetase, isocitrate lyase, catalase, and glycolic oxidase is present in these organelles. The distribution of glyoxysomal enzymes on sucrose density gradients is contrasted with that of the strictly mitochondrial enzymes fumarase, NADH oxidase, and succinoxidase. Malate dehydrogenase and citrate synthetase are present in both organelles. The functional role of glyoxysomes and their relationship to cytosomes from other tissues is discussed.
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PMID:Characterization of glyoxysomes from castor bean endosperm. 1665 30


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