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

The activity of branched-chain aminotransferase in mitochondria isolated from rat tissues was examined, and the mitochondrial contribution to total tissue branched-chain aminotransferase activity was calculated using the mitochondrial marker enzyme citrate synthase. Mitochondrial aminotransferase activity was highest in heart followed by skeletal muscle, kidney and brain. In heart muscle all of the aminotransferase activity was accounted for by the mitochondrial fraction. Activity was found to be mitochondrial in skeletal muscle with high red fiber content and also in kidney cortex. Activity was predominantly cytosolic in brain and muscles with high white fiber composition. Thus, the distribution of branched-chain aminotransferase activity in skeletal muscle was dependent on fiber type. No branched-chain aminotransferase activity was detected in liver mitochondria, and in liver tissue activity was too low to be relevant at physiological concentrations of branched-chain amino acids. Within a tissue, regardless of the subcellular distribution of aminotransferase activity, the relative rates of transamination with subsaturating or "saturating" concentrations of KIV or isoleucine were similar. Finally, amino acid preference was also similar within a tissue, but not necessarily between or among different tissues.
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PMID:Subcellular distribution of branched-chain aminotransferase activity in rat tissues. 321 76

After a prototrophic strain of Staphylococcus aureus had been exposed to diethyl sulfate, 28 isoleucine- and isoleucine-valine-dependent mutants (ilv mutants) were isolated. On the basis of auxanography, their ability to accumulate intermediates of isoleucine and valine biosynthesis, and intergeneric syntrophism with ilv mutants of Salmonella typhimurium, all mutants were placed into four groups, each of which corresponded to a presumed enzymatic deficiency, as follows: group A, deficient in l-threonine deaminase; group B, deficient in the condensing enzyme; group C, deficient in reductoisomerase; group D, deficient in alpha-beta-dihydroxy acid dehydrase. No mutants blocked in the terminal (transaminase) reactions were isolated. Transduction analyses (best-fit, ratio, and complementation tests) with the use of phage 83 established that the linear arrangement of the structural genes is identical with the order of participation of their enzymes in isoleucine and valine biosynthesis, and that these genes comprise a single linkage group which can exist on a single donor fragment during transduction.
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PMID:Biochemical and genetic analysis of isoleucine and valine biosynthesis in Staphylococcus aureus. 602 2

Active-site peptides of acetyl transferase, condensing enzyme and acyl carrier protein in the neighborhood of the prosthetic group, 4'-phosphopantetheine, of Cephalosporium caerulens fatty acid synthetase were investigated. The enzyme was reacted with [14C]acetyl-CoA or [14C]iodoacetamide. 14C-Labeled enzyme was digested with pepsin, trypsin or both. 14C-Labeled peptides were isolated by several purification procedures. The amino acid sequence of the active site of condensing enzyme was determined to be Tyr-Gln-Val-Glu-Ser-Cys-Pro-Ile-Leu-Glu-Gly-Lys and that of acetyl transferase was Phe-Ser-Gly-Ala-Thr-Gly-His-Ser-Gln-Gly. The amino acid composition around the 4'-phosphopantetheine-carrying serine was determined to be Asx2, Thr, Ser, Glx3, Gly2, Ala, Ile, Leu3, and Lys. When these active-site peptides were compared with those of Saccharomyces cerevisiae synthetase, a high degree of homology was observed in the active-site peptides of the acetyl transferase and acyl carrier protein domains. However, that of the condensing enzyme domain gave lower homology. These findings may support the assumption that the low reactivity of cerulenin with C. caerulens synthetase is a consequence of the structure of the condensing enzyme domain.
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PMID:Cerulenin resistance in a cerulenin-producing fungus. III. Studies on active-site peptides of fatty acid synthetase from Cephalosporium caerulens. 654 Jul 72

The gene encoding citrate synthase from a novel bacterial isolate (DS2-3R) from Antarctica has been cloned, sequenced and over expressed in Escherichia coli. Both the recombinant enzyme and the native enzyme, purified from DS2-3R, are cold-active, with a temperature optimum of 31 degrees C. In addition the enzymes are rapidly inactivated at 45 degrees C, and show significant activity at 10 degrees C and below. Comparison of amino acid sequences indicates that DS2-3R citrate synthase is most closely related to the enzyme from gram-positive bacteria. The amino acid sequence of the DS2-3R enzyme shows several features previously recognised in other cold-active enzymes, including an extended surface loop, an increase in the occurrence of charged residues and a decrease in the number of proline residues in loops. Other changes observed in some psychrophilic enzymes, such as a decrease in isoleucine content and in arginine/(arginine+lysine) content, were not seen in this case.
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PMID:Sequencing and expression of the gene encoding a cold-active citrate synthase from an Antarctic bacterium, strain DS2-3R. 931 Mar 59

We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, NADH cytochrome c reductase, succinate dehydrogenase, and succinate cytochrome c reductase were severely deficient. In two of the siblings the enzymatic activity of cytochrome oxidase was mildly decreased (by approximately 50%). Metabolite analysis performed on urine samples taken from these patients revealed high levels of glycine, leucine, valine, and isoleucine, indicating abnormalities of both the glycine-cleavage system and branched-chain alpha-ketoacid dehydrogenase. In contrast, the activities of fibroblast pyruvate carboxylase, mitochondrial aconitase, and citrate synthase were normal. Immunoblot analysis of selected complex III subunits (core 1, cyt c(1), and iron-sulfur protein) and of the pyruvate dehydrogenase complex subunits revealed no visible changes in the levels of all examined proteins, decreasing the possibility that an import and/or assembly factor is involved. To elucidate the underlying molecular defect, analysis of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified as potentially containing the critical region for the unknown gene. This interval maps to region 2p14-2p13.
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PMID:A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13. 1115 34

Oligomerization into multimeric complexes is a prerequisite for the chaperone function of almost all alpha-crystallin type heat shock proteins (alpha-Hsp), but the molecular details of complex assembly are poorly understood. The alpha-Hsp proteins from Bradyrhizobium japonicum are suitable bacterial models for structure-function studies of these ubiquitous stress proteins. They fall into two distinct classes, A and B, display chaperone activity in vitro and form oligomers of approximately 24 subunits. We constructed 19 derivatives containing truncations or point mutations within the N- and C-terminal regions and analyzed them by gel filtration, citrate synthase assay and coaffinity purification. Truncation of more than the initial few amino acids of the N-terminal region led to the formation of distinct dimeric to octameric structures devoid of chaperone activity. In the C-terminal extension, integrity of an isoleucine-X-isoleucine (I-X-I) motif was imperative for alpha-Hsp functionality. This I-X-I motif is one of the characteristic consensus motifs of the alpha-Hsp family, and here we provide experimental evidence of its structural and functional importance. alpha-Hsp proteins lacking the C-terminal extension were inactive, but still able to form dimers. Here, we demonstrate that the central alpha-crystallin domain alone is not sufficient for dimerization. Additional residues at the end of the N-terminal region were required for the assembly of two subunits.
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PMID:A critical motif for oligomerization and chaperone activity of bacterial alpha-heat shock proteins. 1213 98

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. I. Genetic derepression of enzyme formation. J. Bacteriol. 87:566-573. 1964.-A total of 60 mutants of Escherichia coli K-12 resistant to 10(-2)m valine were isolated from the valine-sensitive F' strain AB1206. Conjugation experiments showed that in five of these mutants the valine-resistance locus is closely linked to the structural genes governing isoleucine-valine biosynthesis. In these five valine-resistant mutants, three enzymes of the isoleucine-valine pathway were found to be coordinately derepressed: l-threonine deaminase, dihydroxy acid dehydrase, and transaminase B. Two other enzymes of this pathway, the condensing enzyme and the reductoisomerase, were unaffected. The mutation from valine-sensitivity to valine-resistance appears to have altered an operator locus, because the derepressed state is dominant over the repressed state in diploids heterozygous for the valine-resistance locus. The valine-resistant mutants excrete isoleucine into the medium. The significance of these findings with respect to the valine-sensitivity of E. coli K-12 and the regulation of the biosynthesis of isoleucine and valine by this organism are discussed.
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PMID:REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. I. GENETIC DEREPRESSION OF ENZYME FORMATION. 1412 71

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. II. Identification of two operator genes. J. Bacteriol. 89:654-660. 1965.-A tightly clustered set of five structural genes governs the synthesis of the five enzymes of isoleucine and valine biosynthesis in Escherichia coli. Three of the genes governing transaminase B, dehydrase, and threonine deaminase, are controlled by a single operator locus, designated oprA. The structural gene governing the condensing enzyme is controlled by a second operator locus, designated oprB. Both oprA and oprB have been shown to regulate structural genes which are cis, but not trans, to their own operator. No mutations have yet been found which affect the level of reductoisomerase, but the existence of a third operator controlling the synthesis of this enzyme can be inferred. Enzyme derepression resulting from mutations in oprA confers resistance to high levels of valine. Derepression of the condensing enzyme resulting from mutations in oprB confers resistance to low levels of valine, and to alpha-aminobutyric acid. The significance of these findings with respect to the valine sensitivity of E. coli strain K-12 is discussed.
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PMID:REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. II. IDENTIFICATION OF TWO OPERATOR GENES. 1427 40

Ramakrishnan, T. (Yale University, New Haven, Conn.), and Edward A. Adelberg. Regulatory mechanisms in the biosynthesis of isoleucine and valine. III. Map order of the structural genes and operator genes. J. Bacteriol. 89:661-664. 1965.-A new method has been employed to determine the map order of the structural genes and operator genes governing the enzymes of the isoleucine-valine biosynthetic pathway. This method relies on the observation that phage transduction of markers carried on an F-genote leads to the establishment in the recipient of F-genotes of various lengths. Using this method, we have established that the order of loci is the following: F/ilvE ilvD ilvA oprA/ilvC/ilvB oprB. The operator locus, oprA, regulates the activity of structural genes ilvE (transaminase B), ilvD (dehydrase), and ilvA (threonine deaminase). The operator locus, oprB, regulates the activity of ilvB (condensing enzyme). An operator for ilvC (reductoisomerase) can be inferred to exist, but has not yet been detected genetically. The loci ilvB and oprB have been shown to be at the extreme right end of the sequence, but their positions relative to each other remain to be established.
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PMID:REGULATORY MECHANISMS IN THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. 3. MAP ORDER OF THE STRUCTURAL GENES AND OPERATOR GENES. 1427 41

Ignicoccus hospitalis is an autotrophic hyperthermophilic archaeon that serves as a host for another parasitic/symbiotic archaeon, Nanoarchaeum equitans. In this study, the biosynthetic pathways of I. hospitalis were investigated by in vitro enzymatic analyses, in vivo (13)C-labeling experiments, and genomic analyses. Our results suggest the operation of a so far unknown pathway of autotrophic CO(2) fixation that starts from acetyl-coenzyme A (CoA). The cyclic regeneration of acetyl-CoA, the primary CO(2) acceptor molecule, has not been clarified yet. In essence, acetyl-CoA is converted into pyruvate via reductive carboxylation by pyruvate-ferredoxin oxidoreductase. Pyruvate-water dikinase converts pyruvate into phosphoenolpyruvate (PEP), which is carboxylated to oxaloacetate by PEP carboxylase. An incomplete citric acid cycle is operating: citrate is synthesized from oxaloacetate and acetyl-CoA by a (re)-specific citrate synthase, whereas a 2-oxoglutarate-oxidizing enzyme is lacking. Further investigations revealed that several special biosynthetic pathways that have recently been described for various archaea are operating. Isoleucine is synthesized via the uncommon citramalate pathway and lysine via the alpha-aminoadipate pathway. Gluconeogenesis is achieved via a reverse Embden-Meyerhof pathway using a novel type of fructose 1,6-bisphosphate aldolase. Pentosephosphates are formed from hexosephosphates via the suggested ribulose-monophosphate pathway, whereby formaldehyde is released from C-1 of hexose. The organism may not contain any sugar-metabolizing pathway. This comprehensive analysis of the central carbon metabolism of I. hospitalis revealed further evidence for the unexpected and unexplored diversity of metabolic pathways within the (hyperthermophilic) archaea.
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PMID:Insights into the autotrophic CO2 fixation pathway of the archaeon Ignicoccus hospitalis: comprehensive analysis of the central carbon metabolism. 1740 Jul 48


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