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)

A biotinylated acetyl-CoA carboxylase from the microaerophilic bacterium Helicobacter pylori was partially purified and characterized. The approximate molecular mass of the native enzyme was estimated at 235 kDa by native PAGE. A single band corresponding to approximately 24 kDa was detected by SDS-PAGE, suggesting that the native enzyme is a multi-protein complex. The protein was isolated from the soluble fraction of the cell. Catalytic activity was acetyl-CoA-dependent and inhibited by avidin but unaffected by avidin pretreated with excess biotin. The end-product of the reaction was identified as malonyl-CoA and the reaction was shown to be reversible by NMR spectroscopy. The activity of the enzyme was 0.29 mumol min-1 (mg protein)-1. The Vmax for bicarbonate was calculated at 0.73 mumol min-1 (mg protein)-1, and the affinity of the enzyme for this substrate was relatively low, with an apparent Km of 16.6 mM. These data provide the first evidence of a possible physiological role for the requirement of high levels of CO2 for growth in vitro of this bacterium.
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PMID:Acetyl-CoA carboxylase activity in Helicobacter pylori and the requirement of increased CO2 for growth. 857 4

In Streptomyces coelicolor A3(2), polyketides are made from malonyl-CoA, which is presumed to be derived from acetyl-CoA by the action of acetyl-CoA carboxylase (ACC). No ACC activity was found in cell-free extracts of S. coelicolor. However, propionyl-CoA carboxylase (PCC) activity was detected at substantial levels. Fixation of CO2 by ACC and PCC occurs by covalent bonding of CO2 to a biotin-containing protein. Most bacteria have a single small biotinylated protein of approximately 22 kDa, but S. coelicolor contains three larger biotin-containing proteins (approximately 145, 88 and 70 kDa). To determine which biotinylated protein was associated with PCC activity, the enzyme was purified and shown to comprise an alpha subunit (biotin-containing) of 88 kDa and a beta subunit of 66 kDa. The N-terminal sequences of these proteins were determined and, using an oligonucleotide probe, the gene for the alpha subunit (pccA) was cloned.
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PMID:Propionyl-CoA carboxylase from Streptomyces coelicolor A3(2): cloning of the gene encoding the biotin-containing subunit. 886 40

The autotrophic CO2 fixation pathway in Acidianus brierleyi, a facultatively anaerobic thermoacidophilic archaebacterium, was investigated by measuring enzymatic activities from autotrophic, mixotrophic, and heterotrophic cultures. Contrary to the published report that the reductive tricarboxylic acid cycle operates in A. brierleyi, the enzymatic activity of ATP:citrate lyase, the key enzyme of the cycle, was not detected. Instead, activities of acetyl-CoA carboxylase and propionyl-CoA carboxylase, key enzymes of the 3-hydroxypropionate cycle, were detected only when A. brierleyi was growing autotrophically. We conclude that a modified 3-hydroxypropionate pathway operates in A. brierleyi.
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PMID:Autotrophic carbon dioxide fixation in Acidianus brierleyi. 908 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

The role of carnitine palmitoyltransferase I (CPT-I) in the control of ketogenesis was studied in primary cultures of rat astrocytes. Ketone bodies were the major product of [14C]palmitate oxidation by cultured astrocytes, whereas CO2 made a minor contribution to the total oxidation products. Using tetradecylglycidate as a specific, cell-permeable inhibitor of CPT-I, a flux control coefficient of 0.77 +/- 0.07 was calculated for CPT-I over the flux of [14C]palmitate to ketone bodies. CPT-I from astrocytes was sensitive to malonyl-CoA (IC50 = 3.4 +/- 0.8 microM) and cross-reacted on western blots with an antibody raised against liver CPT-I. On the other hand, astrocytes expressed significant acetyl-CoA carboxylase (ACC) activity, and consequently they contained considerable amounts of malonyl-CoA. Western blot analysis of ACC isoforms showed that ACC in astrocytes--like in neurons, liver, and white adipose tissue--mostly comprised the 265-kDa isoform, whereas the 280-kDa isoform--which was highly expressed in skeletal muscle--showed much lower abundance. Forskolin was used as a tool to study the modulation of the ketogenic pathway in astrocytes. Thus, forskolin decreased in parallel ACC activity and intracellular malonyl-CoA levels, whereas it stimulated CPT-I activity and [14C]palmitate oxidation to both ketone bodies and CO2. Results show that in cultured astrocytes (a) CPT-I exerts a very high degree of control over ketogenesis from palmitate, (b) the ACC/malonyl-CoA/CPT-I system is similar to that of liver, and (c) the ACC/malonyl-CoA/CPT-I system is subject to regulation by cyclic AMP.
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PMID:Role of carnitine palmitoyltransferase I in the control of ketogenesis in primary cultures of rat astrocytes. 975 Nov 93

We have investigated several factors which influence acetyl-CoA carboxylase (ACCase) activity in lysed spinach chloroplasts. (1) When assayed after rapid lysis of light-incubated chloroplasts, ACCase activity was 2-fold higher than activity from dark-incubated chloroplasts. Within 5 min after lysis, activity from dark-incubated chloroplasts increased, suggesting a transient inactivation or inhibition of ACCase in the dark. (2) When lysed chloroplast suspensions were incubated with 30 to 100 microM acetyl-CoA before starting assays, activity was 4-fold higher than if suspensions were not preincubated with acetyl-CoA. CoA, malonyl-CoA, propionyl-CoA, and butyryl-CoA also activated ACCase. Full acetyl-CoA activation required MgATP and was essentially complete after 8 min. ACCase activity decreased upon removal of acetyl-CoA by gel filtration and was partially restored by readdition of acetyl-CoA. Thus, ACCase activation by acetyl-CoA was reversible. (3) Dithiothreitol and thioredoxin stimulated ACCase activity, but only in preparations where ACCase activity was low. (4) ACCase was assayed in concentrations of ATP, ADP, NADPH, NADP+, Mg2+, and CO2/HCO-3, which are estimated to occur in the stroma of chloroplasts under illumination or darkness. ACCase activity from lysed chloroplast suspensions was 10-fold higher when illuminated conditions were used. However, this activity was still 5-fold to 10-fold lower than the rates required to sustain known in vivo rates of fatty acid synthesis and in vitro rates achieved under optimum assay conditions with saturating substrates.
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PMID:Regulation of spinach chloroplast acetyl-CoA carboxylase. 980 58

Mammalian acetyl-CoA carboxylase (ACC) is present in two isoforms, alpha and beta, both of which catalyze formation of malonyl-CoA by fixing CO2 into acetyl-CoA. ACC-alpha is highly expressed in lipogenic tissues whereas ACC-beta is a predominant form in heart and skeletal muscle tissues. Even though the tissue-specific expression pattern of two ACC isoforms suggests that each form may have a distinct function, existence of two isoforms catalyzing the identical reaction in a same cell has been a puzzling question. As a first step to answer this question and to identify the possible role of ACC isoforms in myogenic differentiation, we have investigated in the present study whether the expression and the subcellular distribution of ACC isoforms in H9c2 cardiac myocyte change so that malonyl-CoA produced by each form may modulate fatty acid oxidation. We have observed that the expression levels of both ACC forms were correlated to the extent of myogenic differentiation and that they were present not only in cytoplasm but also in other subcellular compartment. Among the various tested compounds, short-term treatment of H9c2 myotubes with insulin or okadaic acid rapidly increased the cytosolic content of both ACC isoforms up to 2 folds without affecting the total cellular ACC content. Taken together, these observations suggest that both ACC isoforms may play a pivotal role in muscle differentiation and that they may translocate between cytoplasm and other subcellular compartment to achieve its specific goal under the various physiological conditions.
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PMID:Rapid increase of cytosolic content of acetyl-CoA carboxylase isoforms in H9c2 cells by short-term treatment with insulin and okadaic acid. 987 26

The pathway of autotrophic CO2 fixation was studied in the phototrophic bacterium Chloroflexus aurantiacus and in the aerobic thermoacidophilic archaeon Metallosphaera sedula. In both organisms, none of the key enzymes of the reductive pentose phosphate cycle, the reductive citric acid cycle, and the reductive acetyl coenzyme A (acetyl-CoA) pathway were detectable. However, cells contained the biotin-dependent acetyl-CoA carboxylase and propionyl-CoA carboxylase as well as phosphoenolpyruvate carboxylase. The specific enzyme activities of the carboxylases were high enough to explain the autotrophic growth rate via the 3-hydroxypropionate cycle. Extracts catalyzed the CO2-, MgATP-, and NADPH-dependent conversion of acetyl-CoA to 3-hydroxypropionate via malonyl-CoA and the conversion of this intermediate to succinate via propionyl-CoA. The labelled intermediates were detected in vitro with either 14CO2 or [14C]acetyl-CoA as precursor. These reactions are part of the 3-hydroxypropionate cycle, the autotrophic pathway proposed for C. aurantiacus. The investigation was extended to the autotrophic archaea Sulfolobus metallicus and Acidianus infernus, which showed acetyl-CoA and propionyl-CoA carboxylase activities in extracts of autotrophically grown cells. Acetyl-CoA carboxylase activity is unexpected in archaea since they do not contain fatty acids in their membranes. These aerobic archaea, as well as C. aurantiacus, were screened for biotin-containing proteins by the avidin-peroxidase test. They contained large amounts of a small biotin-carrying protein, which is most likely part of the acetyl-CoA and propionyl-CoA carboxylases. Other archaea reported to use one of the other known autotrophic pathways lacked such small biotin-containing proteins. These findings suggest that the aerobic autotrophic archaea M. sedula, S. metallicus, and A. infernus use a yet-to-be-defined 3-hydroxypropionate cycle for their autotrophic growth. Acetyl-CoA carboxylase and propionyl-CoA carboxylase are proposed to be the main CO2 fixation enzymes, and phosphoenolpyruvate carboxylase may have an anaplerotic function. The results also provide further support for the occurrence of the 3-hydroxypropionate cycle in C. aurantiacus.
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PMID:Presence of acetyl coenzyme A (CoA) carboxylase and propionyl-CoA carboxylase in autotrophic Crenarchaeota and indication for operation of a 3-hydroxypropionate cycle in autotrophic carbon fixation. 997 33

The 3-hydroxypropionate cycle, a pathway for autotrophic carbon dioxide fixation, is reviewed with special emphasis on the biochemistry of CO2 fixing enzymes in Acidianus brierleyi, a thermophilic and acidophilic archeon. In the 3-hydroxypropionate cycle, two enzymes, acetyl-CoA carboxylase and propionyl-CoA carboxylase, catalyze CO2 fixation. It has been shown in A. brierleyi, and subsequently in Metallosphaera sedula, that acetyl-CoA carboxylase is promiscuous, acting equally well on acetyl-CoA and propionyl-CoA. The subunit structure of the acyl-CoA carboxylase was shown to be alpha4beta4gamma4. Gene cloning revealed that the genes encoding the three subunits are adjacent to each other. accC encodes the beta-subunit (59 kDa subunit, biotin carboxylase subunit), accB encodes the gamma-subunit (20 kDa subunit, biotin carboxyl carrier protein), and pccB encodes the alpha-subunit (62 kDa subunit, carboxyltransferase subunit). Sequence analyses showed that accC and accB are co-transcribed and that pccB is transcribed separately. Potential biotechnological applications for the 3-hydroxypropionate cycle are also presented.
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PMID:Occurrence, biochemistry and possible biotechnological application of the 3-hydroxypropionate cycle. 1499 52

Biotin is an essential cofactor for a small number of enzymes involved mainly in the transfer of CO2 during HCO-3-dependent carboxylation reactions. This review highlights progress in plant biotin research by focusing on the four major areas of recent investigation: the structure, enzymology, and localization of two important biotinylated proteins (methylcrotonoyl-CoA carboxylase involved in the catabolism of leucine and noncyclic isoprenoids; acetyl-CoA carboxylase isoforms involved in a number of biosynthetic pathways); the biosynthesis of biotin; the biotinylation of biotin-dependent carboxylases, including the characterization of biotin holocarboxylase synthetase isoforms; and the detailed characterization of a novel, seed-specific biotinylated protein. A central challenge for plant biotin research is to determine in molecular terms how plant cells regulate the flow of biotin to sustain the biotinylation of biotin-dependent carboxylases during biosynthetic reactions.
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PMID:BIOTIN METABOLISM IN PLANTS. 1501 85


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