Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to study the problem of how the biomembrane synthesis started in the evolutionary process of the self-reproducing system, we carry out an extensive similarity search of the sequence data stored in databases, using the acetyl-CoA carboxylase, fatty acid synthase and the enzyme proteins leading to the combination of sn-glycerol 3-phosphate and fatty acid as the query sequences. With the use of the FASTA program (Pearson & Lipman, 1988), the proteins that carry an amino acid sequence showing similarity to any of the query sequences are picked up under the criterion of statistical significance of more than 6.0 for the homology, then classified according to the functional blocks where they operate. Finally they are filtered to the enzyme proteins in the metabolic pathways and to the DNA- or RNA-interacting proteins in the translation, transcription and replication apparatuses by eliminating proteins such as membrane proteins, lipase etc. which seem to have been generated after the appearance of the biomembrane. The distribution of the proteins thus selected shows a clear pattern that the amino acid sequences showing considerable similarity to the biomembrane synthetic proteins are concentrically found in the enzyme proteins in and around the section of glycolytic pathway from glyceraldehyde 3-phosphate to pyruvate while the DNA- or RNA-interacting proteins similar to the query sequences are distributed sparsely over the translation, transcription and replication systems. The assignment of similarity regions ascertains that considerable regions of most biomembrane synthetic proteins are covered by the enzyme proteins in and around the glycolytic pathway. Although acetyl-CoA carboxylase and fatty acid synthase are full of variety in the constitution of active domains depending on species, the above-mentioned pattern is also obtained by using either the monofunctional or the multifunctional type of proteins as the query sequences. Thus, the evolution towards biomembrane synthesis may be positioned as an event following the establishment of a section of glycolytic pathway from glyceraldehyde 3-phosphate to pyruvate. The causality of this evolution from the glycolytic pathway to the biomembrane synthesis is also discussed in connection with the absorption of protons released in the glycolytic process.
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PMID:Evolution of the self-reproducing system to the biosynthesis of the membrane: an approach from the amino acid sequence similarity in proteins. 894 44

Three genes coding for different multifunctional acetyl-CoA carboxylase (ACCase; EC 6.4.1.2) isoenzymes from Brassica napus were isolated and divided into two major classes according to structural features in their 5' regions: class I comprises two genes with an additional coding exon of approximately 300 bp at the 5' end, and class II is represented by one gene carrying an intron of 586 bp in its 5' untranslated region. Fusion of the peptide sequence encoded by the additional first exon of a class I ACCase gene to the jellyfish Aequorea victoria green fluorescent protein (GFP) and transient expression in tobacco protoplasts targeted GFP to the chloroplasts. In contrast to the deduced primary structure of the biotin carboxylase domain encoded by the class I gene, the corresponding amino acid sequence of the class II ACCase shows higher identity with that of the Arabidopsis ACCase, both lacking a transit peptide. The Arabidopsis ACCase has been proposed to be a cytosolic isoenzyme. These observations indicate that the two classes of ACCase genes encode plastidic and cytosolic isoforms of multi-functional, eukaryotic type, respectively, and that B. napus contains at least one multi-functional ACCase besides the multi-subunit, prokaryotic type located in plastids. Southern blot analysis of genomic DNA from B. napus, Brassica rapa, and Brassica oleracea, the ancestors of amphidiploid rapeseed, using a fragment of a multi-functional ACCase gene as a probe revealed that ACCase is encoded by a multi-gene family of at least five members.
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PMID:Multi-functional acetyl-CoA carboxylase from Brassica napus is encoded by a multi-gene family: indication for plastidic localization of at least one isoform. 909 17

The intracellular compartmentation of biotin holocarboxylase synthetase has been investigated in pea (Pisum sativum) leaves, by isolation of organelles and fractionation of protoplasts. Enzyme activity was mainly located in cytosol (approx. 90% of total cellular activity). Significant activity was also identified in the soluble phase of both mitochondria and chloroplasts. Two enzyme forms were separated by anion-exchange chromatography. The major form was found to be specific for the cytosol compartment, whereas the minor form was present in mitochondria as well as in chloroplasts. We also report the isolation and DNA sequence of a cDNA encoding an Arabidopsis thaliana biotin holocarboxylase synthetase. This cDNA was isolated by functional complementation of a conditional lethal Escherichia coli birA (biotin ligase gene, which regulates biotin synthesis) mutant. This indicated that the recombinant plant protein was able to biotinylate specifically an essential apoprotein substrate in the bacterial host, that is a subunit of acetyl-CoA carboxylase called biotin carboxyl carrier protein. The full-length nucleotide sequence (1534 bp) encodes a protein of 367 amino acid residues with a molecular mass of 41172 Da and shows specific regions of similarity to other biotin holocarboxylase synthetase genes as isolated from bacteria and yeast, and with cDNA species from human. A sequence downstream of the first translation initiation site encodes a putative peptide structurally similar to organelle-targeting pre-sequences, suggesting a mitochondrial or chloroplastic localization for this isoform.
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PMID:Evidence for multiple forms of biotin holocarboxylase synthetase in pea (Pisum sativum) and in Arabidopsis thaliana: subcellular fractionation studies and isolation of a cDNA clone. 917 80

The product of the retinoblastoma (Rb) susceptibility gene ( RB-1 ) regulates expression of a variety of growth control genes via discrete promoter elements termed retinoblastoma control elements (RCEs). We have previously shown that RCEs are bound and regulated by a common set of ubiquitously expressed nuclear proteins of 115, 95 and 80 kDa, termed retinoblastoma control proteins (RCPs). We have also previously determined that Sp3 and Sp1, two members of the Sp family of transcription factors, encode the 115 and 95 kDa RCPs respectively and that Rb stimulates Sp1/Sp3-mediated transcription in vivo. In this report we have extended these results by determining that the 80 kDa RCP arises from Sp3 mRNA via translational initiation at two internal sites located within the Sp3 trans -activation domain. Internally initiated Sp3 proteins readily bind to Sp1 binding sites in vitro yet have little or no capacity to stimulate transcription of Sp-regulated genes in vivo. Instead, these Sp3-derived proteins function as potent inhibitors of Sp1/Sp3- mediated transcription. Since cell cycle- or signal- induced expression of a variety of genes, including p21 waf1/cip1, p15 INK4B, CYP11A, mdr1 and acetyl-CoA carboxylase, have been mapped to GC-rich promoter elements that bind Sp family members, we speculate that alterations of the protein and/or DNA binding activities of internally initiated Sp3 isoforms may account in part for the regulation of such differentially expressed genes.
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PMID:Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription. 922 12

In euthyroid rats, maximal sympathetic nervous system stimulation (e.g. during cold exposure) results in a 3- to 4-fold increase in brown adipose tissue lipogenesis, a response that is blunted in hypothyroid rats. To further investigate this phenomenon, the role of local type II 5'-deiodinase (5'-DII) was studied in freshly isolated brown adipocytes. In a typical experiment, 1.5 x 10(6) cells were incubated for up to 48 h in a water-saturated 5% CO2-95% O2 atmosphere. After incubation with medium alone or with different concentrations of T4, T3, and/or norepinephrine (NE), lipogenesis was studied by measuring 1) the rate of fatty acid synthesis as reflected by 3H2O incorporation into lipids and 2) the activity of key rate-limiting enzymes, i.e. acetyl coenzyme A carboxylase and malic enzyme, and the results are reported in terms of DNA content per tube. Lipogenesis decreased progressively over time (approximately 40%) when no additions were made to the incubation medium. T4 or T3 partially prevented that inhibition at physiological concentrations (65 x 10[-9] and 0.77 x 10[-9] M, respectively), whereas a receptor-saturating concentration of T3, (154 x 10[-9] M) doubled the lipogenesis rate. The addition of 10(-6) M NE inhibited lipogenesis acutely (approximately 50% by 12 h) and was followed by a progressive stimulation that reached approximately 2-fold by 48 h, but only in the presence of T4. Furthermore, NE did not attenuate T3 (154 x 10[-9] M)-induced lipogenesis. Both the inhibition and the stimulation of lipogenesis caused by NE showed a strong dose-response relationship within the range of 10(-11)-10(-5) M. The role of local 5'-DII was further tested by incubating brown adipocytes with 10(-6) M NE and T4 (65 x 10[-9] M) in the presence of 100 microM iopanoic acid, a potent inhibitor of 5'-DII. Although iopanoic acid did not affect the T3 stimulation of lipogenesis, it did block the approximately 2-fold stimulation of lipogenesis triggered by NE in the presence of T4, confirming the mediation of 5'-DII in this process. In conclusion, lipogenesis in brown adipose tissue is under complex hormonal control, with key roles played by NE, thyroid hormones, and local 5'-DII. As in other tissues, NE-generated signals acutely (12 h) inhibited lipogenesis. However, the presence of the 5'-DII generated enough T3 to stimulate lipogenesis and gradually reverse the short-lived NE-induced inhibition, leading to the 2- to 3-fold response observed at later time points.
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PMID:Thyroxine 5'-deiodination mediates norepinephrine-induced lipogenesis in dispersed brown adipocytes. 944 27

When two copies of the sequences spanning -57 to -35 of the fatty acid synthase (FAS) or -64 to -41 of the ATP citrate-lyase (ACL) gene linked to a reporter gene were transfected into primary cultured hepatocytes, the reporter activities significantly increased in response to insulin/glucose treatment. In cotransfection experiments of the FAS(-57/-35) with the Sp1 or Sp3 expression vector, the reporter activities of transcription were suppressed by Sp1 and stimulated by Sp3. In the cotransfection experiments of ACL(-64/-41), the activities were suppressed by Sp1 but were unchanged by Sp3. A similar effect of Sp1 and Sp3 on transcription was seen in mRNA concentrations and enzyme activities of endogenous FAS and ACL. Moreover, the mRNA concentrations and enzyme activities of endogenous acetyl-CoA carboxylase were suppressed by Sp1 and greatly increased by Sp3. Gel mobility super shift assays using antibodies against Sp1 or Sp3 revealed the binding of the transcription factors Sp1 and Sp3 with the GC rich regions located within FAS(-57/-35) and ACL(-64/-41) genes. The formation of DNA-protein complexes was decreased in rats fed a high-carbohydrate diet in comparison with that in fasted rats, but feeding the corn oil diet inhibited this decrease. In Western immunoblotting assay, however, the amount of Sp1 and Sp3 remained unchanged in the dietary conditions. Therefore, the binding of DNA-protein complexes was not due to changes in the amount of Sp1 and Sp3 but to changes in the binding activity, suggesting that these transcription factors may be an important determinant of lipogenic enzyme expression.
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PMID:Transcriptional regulation of fatty acid synthase gene and ATP citrate-lyase gene by Sp1 and Sp3 in rat hepatocytes(1). 1061 88

Proteins located within the lipid bilayer, surrounding the intracellular bacterial magnetic particles (BMP) from Magnetospirillum sp. AMB-1, were separated using SDS-PAGE. Several major proteins of approximate molecular weight 66.2, 35.6, and 24.8 kDa were identified. The N-terminal amino acid sequence of one of these proteins, designated MpsA, was determined and used to design a pair of PCR primers which amplified a 105 bp DNA fragment from AMB-1 genomic DNA. Gene-walking, using anchored PCR, was used to determine the complete nucleotide sequence (954 bp) of the mpsA gene. The mpsA encodes a 317 amino acid protein which does not have an N-terminal cytoplasmic transport signal sequence. Intracellular localization studies were carried out using an mpsA-luc gene fusion expressed in AMB-1 following gene transfer by conjugation. The gene fusion was constructed by cloning a 1.6 kb mpsA fragment upstream of luc in the conjugal plasmid pKLC. The MpsA-Luc fusion protein was preferentially located on the magnetic particle membrane. Although the function of MpsA remains unknown, homology searches suggest similarity with the alpha subunit of acetyl-CoA carboxylase and the CoA-binding motif.
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PMID:Cloning and characterization of a gene, mpsA, encoding a protein associated with intracellular magnetic particles from Magnetospirillum sp. strain AMB-1. 1067 8

We have cloned a DNA fragment from a genomic library of Myxococcus xanthus using an oligonucleotide probe representing conserved regions of biotin carboxylase subunits of acetyl coenzyme A (acetyl-CoA) carboxylases. The fragment contained two open reading frames (ORF1 and ORF2), designated the accB and accA genes, capable of encoding a 538-amino-acid protein of 58.1 kDa and a 573-amino-acid protein of 61.5 kDa, respectively. The protein (AccA) encoded by the accA gene was strikingly similar to biotin carboxylase subunits of acetyl-CoA and propionyl-CoA carboxylases and of pyruvate carboxylase. The putative motifs for ATP binding, CO(2) fixation, and biotin binding were found in AccA. The accB gene was located upstream of the accA gene, and they formed a two-gene operon. The protein (AccB) encoded by the accB gene showed high degrees of sequence similarity with carboxyltransferase subunits of acetyl-CoA and propionyl-CoA carboxylases and of methylmalonyl-CoA decarboxylase. Carboxybiotin-binding and acyl-CoA-binding domains, which are conserved in several carboxyltransferase subunits of acyl-CoA carboxylases, were found in AccB. An accA disruption mutant showed a reduced growth rate and reduced acetyl-CoA carboxylase activity compared with the wild-type strain. Western blot analysis indicated that the product of the accA gene was a biotinylated protein that was expressed during the exponential growth phase. Based on these results, we propose that this M. xanthus acetyl-CoA carboxylase consists of two subunits, which are encoded by the accB and accA genes, and occupies a position between prokaryotic and eukaryotic acetyl-CoA carboxylases in terms of evolution.
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PMID:Molecular cloning and characterization of two genes for the biotin carboxylase and carboxyltransferase subunits of acetyl coenzyme A carboxylase in Myxococcus xanthus. 1098 50

Apicomplexan parasites such as Toxoplasma gondii contain a primitive plastid, the apicoplast, whose genome consists of a 35-kb circular DNA related to the plastid DNA of plants. Plants synthesize fatty acids in their plastids. The first committed step in fatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACC). This enzyme is encoded in the nucleus, synthesized in the cytosol, and transported into the plastid. In the present work, two genes encoding ACC from T. gondii were cloned and the gene structure was determined. Both ORFs encode multidomain proteins, each with an N-terminal extension, compared with the cytosolic ACCs from plants. The N-terminal extension of one isozyme, ACC1, was shown to target green fluorescent protein to the apicoplast of T. gondii. In addition, the apicoplast contains a biotinylated protein, consistent with the assertion that ACC1 is localized there. The second ACC in T. gondii appears to be cytosolic. T. gondii mitochondria also contain a biotinylated protein, probably pyruvate carboxylase. These results confirm the essential nature of the apicoplast and explain the inhibition of parasite growth in cultured cells by herbicides targeting ACC.
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PMID:Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite Toxoplasma gondii. 1122 7

Milk producers in Malaysia make extensive use of crossbred Sahiwal Friesian dairy cattle. These animals have, however, been found susceptible to lactation failure. A survey of cows in an experimental herd of F1 Sahiwal Friesian animals indicated that, in 30% of animals, milk yield decreased to negligible levels within the first 8 weeks post partum. Lactation failure was associated with a progressive increase in the amount of residual milk left in the udder after normal milking. By week 3 of lactation, residual milk volume was significantly greater than that in animals that, based on previous lactation history were not susceptible to lactation failure, and accounted for up to 30% of milk available at the morning milking. The cellular consequences of residual milk accumulation were evident in the activities of acetyl-CoA carboxylase, fatty acid synthetase and galactosyltransferase, key enzyme markers of cellular differentiation, which decreased in glands undergoing lactation failure and were lower than values measured in tissue of control cows. Mammary cell number, estimated by tissue DNA content, was also reduced in animals undergoing lactation failure. These indices of mammary development indicate that lactation failure is the result of premature involution in susceptible animals. Premature involution is a predictable consequence of progressive milk stasis in failing lactation, and attributable to an increase in autocrine feedback by inhibitory milk constituents. The progressive increase in residual milk is, on the other hand, unlikely to be attributable to impaired mammary development. Measurements of milk storage during milk accumulation showed no differences between control and lactation failure cows in the distribution of milk between alveolar and cisternal storage compartments. We conclude that lactation failure in Sahiwal Friesian cows is due to a failure of milk removal, and probably the result of an impaired milk ejection reflex rather than to the glands' milk storage characteristics.
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PMID:Lactation failure in crossbred Sahiwal Friesian cattle. 1150 81


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