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:6.4.1.2 (acetyl-CoA carboxylase)
2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] is activated by physiological concentrations of CoA. The CoA concentration dependency of this activation is sigmoidal; below 60 microM there is little or no activation, but the activation observed between 60 and 120 microM indicates that small changes in the concentration of CoA can cause significant changes in carboxylase activity. CoA activation of acetyl-CoA crboxylase accompanies polymerization of acetyl-CoA carboxylase. However, the binding site for CoA appears to be different from that of citrate. In contrast to citrate activation, which changes only the Vmax of the reaction, CoA activation of carboxylase results in polymeric forms with a lower Km for acetyl-CoA. The Km for acetyl-CoA is 0.4 mM in the control enzyme, whereas that of the CoA-activated enzyme is as low as 4 microM. The Km for ATP was not changed. Derivatives of CoA were not effective in activating the carboxylase, indicating that the CoA effect is specific. Arguments are presented that CoA could be a physiologically significant positive effector of the carboxylase.
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PMID:Regulation of acetyl-coA carboxylase: properties of coA activation of acetyl-coA carboxylase. 610 89

Fatty acid synthesis is traditionally viewed as being confined to the cytosolic cellular fraction, although a substantial body of data indicates that both microsomes and mitochondria are capable of initiating fatty acid synthesis and may contain acetyl-CoA carboxylase [acetyl-CoA:carbon-doxide ligase (ADP-forming), EC 6.4.1.2], fatty acid synthetase, and ATP-citrate lyase [ATP citrate (pro-3S)-lyase; ATP:citrate oxaloacetate-lyase (pro-3S-CH2COO- leads to acetyl-CoA; ATP-dephosphorylating), EC 4.1.3.8] activities. We have identified 32P-labeled acetyl-CoA carboxylase and 32P-labeled ATP-citrate lyase by immunoprecipitation of a rat hepatocyte microsomal preparation. In the transition between the fasting state (low rates of lipogenesis) and fasting/re-feeding (high rates), the fraction of total cytosolic plus microsomal acetyl-CoA carboxylase in the microsomes increases from 6% to 43%, whereas the microsomal proportion of total fatty acid synthetase and ATP-citrate lyase remains approximately 10%. Microsome isolation conditions favoring carboxylase polymerization (presence of citrate) promote microsomal association, whereas conditions favoring enzyme protomerization (malonyl-CoA, preincubation with cyclic AMP/ATP/Mg2+) diminish this association. The microsomal enzyme has a 5-fold higher specific activity than the cytosolic enzyme as determined by immunotitration. Sucrose density gradient analysis of the microsomal fraction indicates that a substantial portion of carboxylase activity sediments with marker enzymes for endoplasmic reticulum, plasma membrane, Golgi apparatus, and outer mitochondrial membrane, while cytosolic enzyme or isolated enzyme incubated under polymerizing conditions does not penetrate the gradient. These data suggest that the microsomes may be a significant locus of fatty acid synthesis initiated with association of acetyl-CoA carboxylase polymer with this fraction.
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PMID:Microsomal acetyl-CoA carboxylase: evidence for association of enzyme polymer with liver microsomes. 611 83

An endotoxin-induced mediator from exudate cells markedly suppresses the activities of the key enzymes for de novo fatty acid biosynthesis--acetyl-CoA carboxylase [acetyl-CoA:carbon dioxide ligase (ADP-forming), EC 6.4.1.2] and fatty acid synthetase--in differentiating 3T3-L1 murine preadipocytes. The loss in activity, at least in part, appears to be due to a specific effect on the synthesis of the enzymes, as determined by a decreased incorporation of [35S]methionine into immunoadsorbable acetyl-CoA carboxylase and fatty acid synthetase when the cells were exposed to the mediator. During this exposure, the radiolabeling of proteins with [35S]methionine in a particulate fraction was decreased by nearly 50% with little change in the soluble protein fraction. Sodium dodecyl sulfate/polyacrylamide gel analysis of the labeled protein indicated no major disturbances of protein synthesis in general; however, the syntheses of specific proteins in both the soluble and particulate fractions were enhanced or depressed. The present study demonstrates that endotoxin promotes the release of a mediator from exudate cells that regulates key anabolic activities in adipose cells.
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PMID:Selective inhibition of synthesis of enzymes for de novo fatty acid biosynthesis by an endotoxin-induced mediator from exudate cells. 613 82

Preparations of acetyl-CoA carboxylase [acetyl-CoA-carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] have been obtained from the plastids of avocado (Persea americana) fruit mesocarp and from spinach (Spinacia oleracea) chloroplasts. Both preparations required bovine serum albumin, HCO3-, citrate and glycerol for stabilization. The molecular weight of the avocado enzyme was about 6.5 X 10(5) on the basis of 1 mol of biotin/mol of enzyme, the behaviour of both enzymes on gel filtration being in accord with such a value. Removal of the stabilizing bovine serum albumin resulted in the loss of a biotin-containing fragment from the avocado enzyme. Citrate stabilized the enzyme at 10 mM and activated it optimally at 3.0 mM, effecting an approx. 2-fold increase in Vmax. It is suggested that in vivo the enzyme may be located within the chloroplast lamellae.
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PMID:Acetyl-coenzyme A carboxylase from avocado (Persea americana) plastids and spinach (Spinacia oleracea) chloroplasts. 614 8

The subcellular distribution of acetyl-CoA carboxylase [acetyl-CoA-carbon dioxide ligase (ADP-forming), EC 6.4.1.2] was determined in mesophyll protoplasts isolation from barley, a C3 plant, and sorghum, a C4 plant. In both species, all of the mesophyll acetyl-CoA carboxylase was demonstrated to be chloroplastic. In barley leaves and mesophyll protoplasts, a single biotinyl protein of 60,000 Da was identified by a modified Western-blotting procedure. The subcellular distribution of this biotinyl protein was identical to that found for acetyl-CoA carboxylase. These results are discussed in relation to the compartmentation of reactions requiring malonyl-CoA as a substrate.
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PMID:Subcellular distribution of acetyl-coenzyme A carboxylase in mesophyll cells of barley and sorghum leaves. 615 78

Pyruvate carboxylase (PC) was purified to homogeneity from an overexpressing strain of the purple photosynthetic bacterium Rhodobacter capsulatus using a rapid dye-ligand affinity chromatography procedure, in which dye-bound enzyme was specifically eluted with a low concentration of acetyl-CoA, an allosteric activator of the enzyme. The enzyme purified by this method was obtained in 75% yield with a specific activity of 40 U (mg protein)-1. In contrast, affinity chromatography on a monomeric avidin column, commonly used in the purification of biotin-containing carboxylases, resulted in a yield of < 40%, with a specific activity of 10 U (mg protein)-1. The enzyme purified by the dye-linked procedure had a subunit molecular mass of 140,000 Da and was absolutely dependent on acetyl-CoA for activity. Acetyl-CoA was also effective in protecting the enzyme from thermal denaturation. The enzyme was inhibited by 2-oxoglutarate and, to a lesser extent, L-aspartate, with sigmoidal kinetics with respect to acetyl-CoA concentration. The amino acid composition, pH optimum and kinetic constants for pyruvate, ATP and bicarbonate were determined. An N-terminal sequence of 26 residues was obtained, which was homologous to the N-terminal regions of several eukaryotic PCs, propionyl-CoA carboxylases and acetyl-CoA carboxylase.
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PMID:Acetyl-CoA-dependent pyruvate carboxylase from the photosynthetic bacterium Rhodobacter capsulatus: rapid and efficient purification using dye-ligand affinity chromatography. 758 22

Acetyl-CoA carboxylase [ACCase; acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] catalyzes the ATP-dependent carboxylation of acetyl CoA to produce malonyl CoA. In plants, malonyl CoA is needed for plastid localized fatty acid biosynthesis and for a variety of pathways in the cytoplasm including flavonoid biosynthesis. We have determined the full nucleotide sequence of an ACCase from alfalfa, which appears to represent a cytoplasmic isozyme. Partial cDNAs were isolated from a cDNA library of suspension culture cells that had been elicited for isoflavonoid phytoalexin synthesis. The full-length sequence was obtained by primer extension and amplification of the cDNA with synthetic primers. The sequence codes for a protein of 2257 amino acids with a calculated M(r) of 252,039. The biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase domains, respectively, show approximately 72%, 50%, and 65% sequence similarity to those of animal, diatom, and yeast ACCase sequences. ACCase enzyme activity and transcripts are induced severalfold upon addition of yeast or fungal elicitors to alfalfa cell cultures.
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PMID:Molecular cloning, characterization, and elicitation of acetyl-CoA carboxylase from alfalfa. 791 Apr 6

We describe the construction of ribozyme genes that are specific to acetyl-CoA carboxylase [ACC; acetyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] mRNAs and the effects of their expression on long-chain fatty acid synthesis. In a cell-free system, these ribozymes precisely cleave ACC mRNA at the expected sites. 30A5 preadipocyte cells stably transfected with the ribozyme gene show a substantial reduction in the amount of ACC mRNA as compared to non-ribozyme-expressing cells. The decrease in ACC mRNA was associated with a significant decrease in ACC enzyme activity, and the rate of fatty acid synthesis fell to about 30-70% of the control. When these cells are induced to differentiate into adipocytes, lipid accumulation is very slow in comparison with control cells. The activity of fatty acid synthase and the mRNA level of beta-actin were not affected. These data indicate that ribozymes designed to specifically target ACC mRNA under in vivo conditions act by decreasing the ACC mRNA level, which, in turn, decreases fatty acid synthesis.
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PMID:Inhibition of fatty acid synthesis by expression of an acetyl-CoA carboxylase-specific ribozyme gene. 793 24

The complete amino acid sequence of 3T3-L1 adipocyte pyruvate carboxylase (PC) [pyruvate:carbon-dioxide ligase (ADP-forming), EC 6.4.1.1] has been deduced from sequencing overlapping cDNA clones obtained from an adipocyte cDNA library constructed in the lambda Zap vector. The encoding mRNA for PC promoter contains 4067 nt, including a 3534-nt coding sequence and noncoding regions of 100 and 433 nt at the 5' and 3' ends, respectively. The biotinylated lysine of the encoded PC promoter (1178 amino acids with a calculated M(r) of apocarboxylase = 129,784) is located 35 residues from the COOH-terminal end and, as in most other biotin enzymes, is in the consensus sequence AMKM. The adipocyte PC is closely similar (53% identity) to the yeast enzyme and contains different segments that are homologous with regions from the biotin carboxylase component of Escherichia coli acetyl-CoA carboxylase, the keto acid-binding subunits of Propionibacterium shermanii oxaloacetate transcarboxylase and Klebsiella pneumoniae oxaloacetate decarboxylase, and to the biotin carboxyl-carrier protein of the bacterial biotin enzymes. In addition to the putative mitochondrial targeting signal, functional domains are readily identifiable in the sequence and are in the following order: biotin carboxylase-carboxyltransferase-biotin carboxyl-carrier protein, as proposed for yeast PC.
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PMID:Adipose pyruvate carboxylase: amino acid sequence and domain structure deduced from cDNA sequencing. 844 88

An entire gene encoding wheat (var. Hard Red Winter Tam 107) acetyl-CoA carboxylase [ACCase; acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] has been cloned and sequenced. Comparison of the 12-kb genomic sequence with the 7.4-kb cDNA sequence reported previously revealed 29 introns. Within the coding region, the exon sequence is 98% identical to the known wheat cDNA sequence. A second ACCase gene was identified by sequencing fragments of genomic clones that include the first two exons and the first intron. Additional transcripts were detected by 5' and 3' RACE analysis (rapid amplification of cDNA ends). One set of transcripts had a 5' end sequence identical to the cDNA found previously and another set was identical to the gene reported here. The 3' RACE clones fall into four distinguishable sequence sets, bringing the number of ACCase sequences to six. None of these cDNA or genomic clones encodes a chloroplast targeting signal. Identification of six different sequences suggests that either the cytosolic ACCase genes are duplicated in the three chromosome sets in hexaploid wheat or that each of the six alleles of the cytosolic ACCase gene has a readily distinguishable DNA sequence.
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PMID:Structure of a gene encoding a cytosolic acetyl-CoA carboxylase of hexaploid wheat. 870 Aug 51


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