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)

Chicken liver fatty acid synthase is inhibited by the thiol-modifying reagents 5,5'-dithiobis-(2-nitrobenzoic acid) and iodoacetamide. Total inactivation of the activity for fatty acid synthesis requires the modification of about 8 of the nearly 50 freely accessible thiol groups per molecule. The differential binding of iodo[14C]acetamide to phenylmethylsulphonyl fluoride-modified enzyme in the absence and in the presence of excess acetyl-CoA shows complete modification of one cysteine-SH site of the condensing enzyme and partial modification of the pantetheine-SH site for a total of approx. 1.4 mol of iodoacetamide bound per mol of enzyme. The reaction of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) generates disulphide cross-links for each molecule of the reagent added, but 95% of these cross-links are intrasubunit. Both the iodoacetamide- and 5,5'-dithiobis-(2-nitrobenzoic acid)-modified species catalyse all the component partial reactions of fatty acid synthesis except the condensation reaction. The results obtained with iodoacetamide show that in the dimeric fatty acid synthase modification of one cysteine-SH condensing site and/or one pantetheine-SH site per dimer is sufficient to affect inhibition of condensing activity and the activity for fatty acid synthesis, and are in accord with a recently proposed model for the mechanism of action of animal fatty acid synthases [Kumar (1982) J. Theor. Biol. 95, 263-283].
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PMID:Inhibition of the condensing component of chicken liver fatty acid synthase by iodoacetamide and 5,5'-dithiobis-(2-nitrobenzoic acid). 666 Nov 83

In contrast with other tissues, the nervous system is very rich in lipids, most of which are found in membranes. Fatty acids thus play a role in membrane structure and function: sphingolipids are essentially found in myelin and present original fatty acid patterns. Saturated and monounsaturated fatty acids are synthesized in microsomes by 3 different systems which differ at the level of the condensing enzyme. The activities of these systems are directly related to myelination. Mitochondria are also able to synthesize fatty acids but the pathways are totally different and unrelated to myelination. Moreover, the brain does not elaborate all its membrane fatty acids whose exogenous origin is demonstrated by injecting labelled non-essential fatty acids. The relationship between blood and brain vary during brain development; the uptake of fatty acids is quantitatively very important during glial cell multiplication and myelination. Nutrition alters the fatty acid composition of brain membranes; the fatty acids are largely altered in an opposite way in the neurons and oligodendrocytes of hypotrophic animals.
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PMID:[Biochemistry of brain lipids (especially fatty acids). In situ synthesis and exogenous origin during development. Various aspects of nutritional effects]. 676 Feb 99

Brain contains two families of fatty acids, their localization and thus their function are different. Polyunsaturated fatty acids are mainly found in grey matter and are related to neuronal activity: C20:4 and C22:6 (omega 6 and omega 3, respectively) are quantitatively very important; it is not known if their synthesis occurs in situ (from C18 - essential fatty acids only in trace amount in brain) or if they originate from an extracerebral pool. Saturated fatty acids are mainly found in myelin. Saturated fatty acid biosynthesis occurs in three subcellular comportments: cytosol, mitochondria and endoplasmic reticulum: the same enzymes elongate saturated as well as monounsaturated homologues. In contrast the synthesis of polyunsaturated fatty acids is hardly known: elongation-desaturation mechanisms shown in the liver are also possibly present in the brain. The regulation of fatty acid biosynthesis is studied at two levels: --level of metabolic pathways: occurence of elongation is related to cell differciation, lipidic receptors being also involved; --level of enzymatic activities: elongation is the result of successive reaction and regulation is acting on condensing enzyme for saturated fatty acid biosynthesis, this enzyme determines kinetics of the overall chain lengthening and the chain length specificity.
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PMID:[Elongation of fatty acids in the nervous system]. 700 97

In chronic experimental and human pyelonephritis (PN) renal enzyme and phosphatide analyses and quantitative histological examinations were performed. The results reported in this study only refer to citrate-synthase activities (= condensing enzyme = CE). 139 rabbits developed unilateral experimental pyelonephritis, in further 19 rabbits the experimental PN did not settle or "healed up spontaneously". 31 samples of human pyelonephritic nephrocirrhotic kidneys and 20 samples of healthy human kidneys were examined in the same manner. The glomerular CE-activities in the rabbit increased steeply in the 20- and 31-days-series, remained at a high level up to the 100-days-series, showed normal values in the 213-days-series, and permitted a marked decrease to be seen in the 261-days-series only. The corticotubular CE-activities increased steeply in the 20- and 31-day-series, still being above the normal values in the 64-days-series. Thereafter, only reduced and strongly reduced values were observed. In the pyelonephritic medulla of rabbits the CE-activities increased very steeply during the 20-days-series, were still above the level of the normal values up to the 100-days-series, dropping then to pathologically reduced data in the 212-days-series. Thus the CE-activities showed a similar type of behaviour to that of the corresponding glomeruli. Chronically pyelonephritic contracted renal tissue in human beings also showed major reductions in CE-activities in all three tissue fractions studies. The significance calculations (universally applied t-test) showed an overwhelming majority of significant values (p less than 0.001).
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PMID:Citrate-synthase activities in the renal tissue during experimental and chronic human pyelonephritis. 725 Feb 98

The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fatty acids in the seed. The product of the FAE1 gene is presumed to be a condensing enzyme that extends the chain length of fatty acids from C18 to C20 and C22. We report here the cloning of FAE1 by directed transposon tagging with the maize element Activator (Ac). An unstable fae1 mutant was isolated in a line carrying Ac linked to the FAE1 locus on chromosome 4. Cosegregation and reversion analyses established that the new mutant was tagged by Ac. A DNA fragment flanking Ac was cloned by inverse polymerase chain reaction and used to isolate FAE1 genomic clones and a cDNA clone from a library made from immature siliques. The predicted amino acid sequence of the FAE1 protein shares homology with those of other condensing enzymes (chalcone synthase, stilbene synthases, and beta-ketoacyl-acyl carrier protein synthase III), supporting the notion that FAE1 is the structural gene for a synthase or condensing enzyme. FAE1 is expressed in developing seed, but not in leaves, as expected from the effect of the fae1 mutation on the fatty acid compositions of those tissues.
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PMID:Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene with the maize transposon activator. 773 65

The genes encoding all enzymes necessary for capsular polysaccharide biosynthesis in Neisseria meningitidis B are located on a 5 kb DNA fragment within the chromosomal cps gene cluster. Nucleotide sequence analysis revealed four open reading frames (ORFs), which can encode proteins with molecular masses of 41.4 kDa, 24.9 kDa, 38.3 kDa, and 54.4 kDa, respectively. These ORFs constitute a transcriptional unit as demonstrated by Northern blots. Primer extension analysis revealed that the transcriptional start site is preceded by a nucleotide sequence with homologies to the sigma 70 consensus promoter sequence of Escherichia coli. Functional analysis of the proteins encoded by the ORFs indicated that ORF2 encodes the CMP-NeuNAc synthetase, ORF3 encodes the NeuNAc condensing enzyme, and ORF4 encodes the alpha-2,8 polysialyltransferase. ORF1 encodes an enzyme, which provides a precursor molecule for synthesis of monomeric NeuNAc. In E. coli the subcloned ORFs 2-4 were able to synthesize a high-molecular-weight alpha-2,8 polysialic acid. In contrast, inactivation of ORF1 in the meningococcal genome resulted in a complete loss of capsule production. A regulatory enzyme, the CMP-NeuNAc hydrolase, which cleaves CMP-NeuNAc to CMP and NeuNAc, was not found as a part of the capsular polysaccharide biosynthesis gene operon or within the cps gene cluster.
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PMID:Molecular analysis of the biosynthesis pathway of the alpha-2,8 polysialic acid capsule by Neisseria meningitidis serogroup B. 783 May 52

A fourth fatty acid condensing enzyme was isolated from Escherichia coli by its ability to restore elongating activity to a protein extract which had been treated with cerulenin, a condensing enzyme-specific inhibitor. The purified beta-ketoacyl-[acyl carrier protein] (ACP) synthase IV [3-oxoacyl-ACP synthase; acyl-ACP:malonyl-ACP C-acyltransferase (decarboxylating), EC 2.3.1.41] (KAS IV) is specific for short-chain acyl-ACP substrates. The enzyme is stable at 43 degrees C and very sensitive to cerulenin (50% inhibition at 3 microM), which binds covalently. A condensing enzyme-specific antibody raised to an expressed open reading frame from barley was used to identify KAS IV protein in Western blots, and the sequence obtained for 30 amino-terminal residues. This led to the isolation of the fabJ gene located in the fab cluster at 24.8 min of the E. coli chromosome. The fabJ gene encodes a polypeptide of 413 amino acids and molecular mass 43 kDa that shows 38% identity and 64% similarity to the fabB-encoded KAS I. The amino acid sequence of KAS IV, however, is more similar to all other published condensing enzyme sequences than the KAS I sequence is. A specialized putative function for this enzyme is to supply the octanoic substrates for lipoic acid biosynthesis. We predict that an analogue of KAS IV with the same function will be found in plant mitochondria. The described complementation assay can be used to detect condensing enzymes with other substrate specificities by supplementing the cerulenin-treated extract with appropriate purified KAS enzymes.
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PMID:The fabJ-encoded beta-ketoacyl-[acyl carrier protein] synthase IV from Escherichia coli is sensitive to cerulenin and specific for short-chain substrates. 797 2

A genomic DNA sequence of Streptomyces strain ISP 5485 was cloned, sequenced and compared with corresponding information from nuclei acid data banks. The DNA sequence was unique, but showed homology to DNA coding for the condensing enzyme, 2-oxoacyl synthase, of the deoxyerythronolide B synthase complex (DEBS) from Saccharopolyspora erythraea NRRL 2338. A subfragment of the sequenced DNA was used to construct a gene-specific probe that formed part of the putative 2-oxoacyl synthase gene. The PCR-amplified and labelled probe was used in hybridization experiments involving 33 streptomycete strains that produced different classes of antibiotics. The probe showed widespread homology with DNA considered to be part of analogous genes within genomes of different polyketide producers. The implications of the probe homology to bacterial chromosomal DNA are discussed.
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PMID:Distribution of oxoacyl synthase homology sequences within Streptomyces DNA. 802 Jul 54

Cerulenin, an antifungal antibiotic produced by Cephalosporium caerulens, is a potent inhibitor of fatty acid synthase in various organisms, including Saccharomyces cerevisiae. The antibiotic inhibits the enzyme by binding covalently to the active center cysteine of the condensing enzyme domain. We isolated 12 cerulenin-resistant mutants of S. cerevisiae following treatment with ethyl methanesulfonate. The mechanism of cerulenin resistance in one of the mutants, KNCR-1, was studied. Growth of the mutant was over 20 times more resistant to cerulenin than that of the wild-type strain. Tetrad analysis suggested that all mutants mapped at the same locus, FAS2, the gene encoding the alpha subunit of the fatty acid synthase. The isolated fatty acid synthase, purified from the mutant KNCR-1, was highly resistant to cerulenin. The cerulenin concentration causing 50% inhibition (IC50) of the enzyme activity was measured to be 400 microM, whereas the IC50 value was 15 microM for the enzyme isolated from the wild-type strain, indicating a 30-fold increase in resistance to cerulenin. The FAS2 gene was cloned from the mutant. Sequence replacement experiments suggested that an 0.8 kb EcoRV-HindIII fragment closely correlated with cerulenin resistance. Sequence analysis of this region revealed that the GGT codon encoding Gly-1257 of the FAS2 gene was altered to AGT in the mutant, resulting in the codon for Ser. Furthermore, a recombinant FAS2 gene, in which the 0.8 Kb EcoRV-HindIII fragment of the wild-type FAS2 gene was replaced with the same region from the mutant, when introduced into FAS2-defective S. cerevisiae complemented the FAS2 phenotype and showed cerulenin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerulenin-resistant mutants of Saccharomyces cerevisiae with an altered fatty acid synthase gene. 804 67

1. Viable myocytes were obtained from rat hearts. Oxidation of [1-14C]palmitate by these cells could be decreased by the addition of glucose (5 mM) or lactate (2 mM). In the presence of glucose, insulin decreased and adrenaline increased palmitate oxidation. 2. The myocytes contained activities of ATP citrate-lyase, acetyl-CoA carboxylase and the condensing enzyme of the fatty acid elongation system. No fatty acid synthase activity was demonstrable in myocytes. 3. In rat hearts perfused with 5 mM glucose, malonyl-CoA content was acutely raised by insulin. In the presence of glucose+insulin, perfusion with palmitate or adrenaline decreased the malonyl-CoA content. 4. It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated. This is likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart.
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PMID:Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation. 821 40


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