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)

The hypothesis is advanced that NADP(+)-malic enzyme (ME; EC 1.1.1.40) is an important activity in regulating the extent of lipid accumulation in filamentous fungi. In Mucor circinelloides, a fungus capable of accumulating only 25% (w/w, dry wt) lipid, even under the most propitious conditions, ME disappears 15-20 h after nitrogen exhaustion, coincident with the cessation of lipid accumulation. In contrast, ME in Mortierella alpina, a fungus capable of accumulating 50% (w/w, dry wt) lipid, remains active for over 60 h after N-exhaustion during which time lipid accumulation continues. No other enzyme activity studied, including the lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase, diacyglycerol acyltransferase, ATP: citrate lyase and the NADPH-generating enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP+:isocitrate dehydrogenase, demonstrated any correlation with the accumulation of storage lipid in either fungus. Full activity of ME is restored in Mr. circinelloides within 4 h by adding NH4+ to the cultures, but this is prevented by adding cycloheximide as an inhibitor of protein synthesis. This suggests that the decrease in ME activity occurs due to down-regulation of the ME gene.
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PMID:The role of malic enzyme in the regulation of lipid accumulation in filamentous fungi. 1046 57

The relevance of Ca2+-calmodulin-mediated processes in channelling acetate for aflatoxin formation was investigated by studying the influence of trifluoperazine (an anticalmodulin agent) on [14C]-acetate incorporation and activity of acetyl-CoA carboxylase in Aspergillus parasiticus NRRL 2999. Culturing the organism in presence of 0.14 mmol l-1 trifluoperazine resulted in 55% decrease of [14C]-acetate incorporation into aflatoxin B1, along with an 80% decrease in acetyl-CoA carboxylase activity at periods corresponding to maximal aflatoxin production. Concomitant decrement (35%) in the activity of glucose-6-phosphate dehydrogenase indicated decreased availability of reduction potential (NADPH) required for aflatoxin biosynthesis. The ability of calmodulin to activate and trifluoperazine to inhibit acetyl-CoA carboxylase activity in a dose-dependent manner was also noted under in vitro conditions. The combined results suggest calmodulin-mediated activation of acetyl-CoA carboxylase as an important event for aflatoxin production.
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PMID:Calmodulin mediated activation of acetyl-CoA carboxylase during aflatoxin production by Aspergillus parasiticus. 1079 46

To gain insights into the regulation of fat synthesis, we have investigated the effect of cold environmental exposure and feed restriction of sheep on activity and immunodetectable protein content of acetyl-CoA carboxylase (ACC) and fatty acid synthase in adipose tissue. Subcutaneous and mesenteric adipose tissues were collected at slaughter from sheep exposed to either cold (0+/-2 degrees C) or warm (23+/-2 degrees C) environment, and given either ad libitum or restricted access to feed for three 5-wk periods. Acetyl-CoA carboxylase was isolated from frozen adipose tissue samples and activity determined as the rate of incorporation of H14CO3- into acid stable malonyl-CoA. Cold exposure and feed restriction reduced (P < .05) ACC activity in the two adipose tissue depots. Western blot analysis with peroxidase-conjugated streptavidin showed that both adipose tissue depots express a single isoform of ACC. In s.c. adipose tissue, cold exposure increased (P < .05) ACC protein abundance, which is opposite to the change in activity. However, feed restriction reduced immunodetectable ACC protein. There was no significant effect of environment or feeding level on ACC protein abundance in mesenteric tissue. Fatty acid synthase activity determined in ammonium sulfate extract by measuring the malonyl-CoA- and acetyl-CoA-dependent oxidation of NADPH was decreased (P < .05) by feed restriction in both s.c. and mesenteric tissues. Cold exposure reduced fatty acid synthase activity in s.c. but not in mesenteric tissue. There was no effect of environment on fatty acid synthase protein abundance in either adipose tissue depot. However, feed restriction significantly reduced fatty acid synthase protein abundance in the two depots. The data suggest that feed restriction and exposure of ruminants to cold environmental conditions may significantly down-regulate the activity of key lipogenic enzymes.
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PMID:Acetyl-CoA carboxylase and fatty acid synthase activity and immunodetectable protein in adipose tissues of ruminants: effect of temperature and feeding level. 1098 14

The 3-hydroxypropionate cycle is a new autotrophic CO(2) fixation pathway in Chloroflexus aurantiacus and some archaebacteria. The initial step is acetyl-coenzyme A (CoA) carboxylation to malonyl-CoA by acetyl-CoA carboxylase, followed by NADPH-dependent reduction of malonyl-CoA to 3-hydroxypropionate. This reduction step was studied in Chloroflexus aurantiacus. A new enzyme was purified, malonyl-CoA reductase, which catalyzed the two-step reduction malonyl-CoA + NADPH + H(+) --> malonate semialdehyde + NADP(+) + CoA and malonate semialdehyde + NADPH + H(+) --> 3-hydroxypropionate + NADP(+). The bifunctional enzyme (aldehyde dehydrogenase and alcohol dehydrogenase) had a native molecular mass of 300 kDa and consisted of a single large subunit of 145 kDa, suggesting an alpha(2) composition. The N-terminal amino acid sequence was determined, and the incomplete gene was identified in the genome database. Obviously, the enzyme consists of an N-terminal short-chain alcohol dehydrogenase domain and a C-terminal aldehyde dehydrogenase domain. No indication of the presence of a prosthetic group was obtained; Mg(2+) and Fe(2+) stimulated and EDTA inhibited activity. The enzyme was highly specific for its substrates, with apparent K(m) values of 30 microM malonyl-CoA and 25 microM NADPH and a turnover number of 25 s(-1) subunit(-1). The specific activity in autotrophically grown cells was 0.08 micromol of malonyl-CoA reduced min(-1) (mg of protein)(-1), compared to 0.03 micromol min(-1) (mg of protein)(-1) in heterotrophically grown cells, indicating downregulation under heterotrophic conditions. Malonyl-CoA reductase is not required in any other known pathway and therefore can be taken as a characteristic enzyme of the 3-hydroxypropionate cycle. Furthermore, the enzyme may be useful for production of 3-hydroxypropionate and for a coupled spectrophotometric assay for activity screening of acetyl-CoA carboxylase, a target enzyme of potent herbicides.
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PMID:Malonyl-coenzyme A reductase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycle for autotrophic CO(2) fixation. 1194 53

Various inorganic and organic nitrogen sources were used to compare their effects on the lipogenesis and the activities of lipogenic enzymes (providing acetyl-CoA and donating NADPH) in gamma-linolenic acid-producing fungus Cunninghamella echinulata. Lipid accumulation was enhanced by organic nitrogen, among them the presence of corn-steep led to almost 40% oil in the biomass. While organic nitrogen increased activities of acetyl-CoA carboxylase (ACC) and malic enzyme (ME), ATP:citrate lyase (ACL) was rapidly enhanced by ammonium ion. The use of NaNO(3) resulted in high activities of glucose 6-phosphate dehydrogenase (GPD) and 6-phosphogluconate dehydrogenase (PGD). NADP-isocitrate dehydrogenase (NADP-ICD) was more active when the fungus utilized all inorganic N-compounds. The rise of nitrogen concentration in medium was accompanied with reduced lipid accumulation and a fall of ACL, ACC, and ME. In contrast, N-sufficient conditions favored biomass growth and elevated activities of GPD and PGD. Kinetic experiments also suggest that a significant portion of the required acetyl-CoA was being provided via ACL and ACC, and ME (probably coupled with GPD) channeled the NADPH into the fatty acid biosynthesis. The contribution of the lipogenic enzymes to metabolic pathways other than lipogenesis is also discussed.
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PMID:Effect of nitrogen sources on the activities of lipogenic enzymes in oleaginous fungus Cunninghamella echinulata. 1250 58

Thioredoxin-interacting protein (Txnip) is a ubiquitous protein that binds with high affinity to thioredoxin and inhibits its ability to reduce sulfhydryl groups via NADPH oxidation. HcB-19 mice contain a nonsense mutation in Txnip that eliminates its expression. Unlike normal animals, HcB-19 mice have approximately 3-fold increase in insulin levels when fasted. The C-peptide/insulin ratio is normal, suggesting that the hyperinsulinemia is due to increased insulin secretion. Fasted HcB-19 mice are hypoglycemic, hypertriglyceridemic, and have higher than normal levels of ketone bodies. Ablation of pancreatic beta-cells with streptozotocin completely blocks the fasting-induced hypoglycemia/hypertriglyceridemia, suggesting that these abnormalities are due to excess insulin secretion. This is supported by increased hepatic mRNA levels of the insulin-inducible, lipogenic transcription factor sterol-responsive element-binding protein-1c and two of its targets, acetyl-CoA carboxylase and fatty acid synthase. During a prolonged fast, the hyperinsulinemia up-regulates lipogenesis but fails to down-regulate hepatic phosphoenolpyruvate carboxykinase mRNA expression. Hepatic ratios of reduced:oxidized glutathione, established regulators of gluconeogenic/glycolytic/lipogenic enzymes, were elevated 30% in HcB-19 mice, suggesting a loss of Txnip-enhanced sulfhydryl reduction. The altered hepatic enzymatic profiles of HcB-19 mice divert phosphoenolpyruvate to glyceroneogenesis and lipogenesis rather than gluconeogenesis. Our findings implicate Txnip-modulated sulfhydryl redox as a central regulator of insulin secretion in beta-cells and regulation of many of the branch-points of gluconeogenesis/glycolysis/lipogenesis.
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PMID:Mice lacking thioredoxin-interacting protein provide evidence linking cellular redox state to appropriate response to nutritional signals. 1504 87

This paper describes the antitumoral activity of branched-chain fatty acid (BCFA) in human breast cancer cells with an emphasis on its effect on fatty acid biosynthesis. First, the relationship between chain-length and antitumoral activity was studied. The highest activity was observed with iso-16:0, and the activity decreased with increase or decrease of the chain-lengths from C16:0. Anteiso-BCFA, as well as iso-series, was cytotoxic to the breast cancer cells. Cytotoxicity of BCFA was comparable to that of conjugated linoleic acid known as antitumoral fatty acid. Incubation of breast cancer cells with BCFA (13-methyltetradecanoic acid) significantly reduced the [14C] acetate incorporation into free fatty acid and fatty acid esters, showing the inhibition of fatty acid biosynthesis by BCFA. Examination of substrate level effect found that BCFA slightly inhibited fatty acid synthetase and acetyl-CoA carboxylase, and significantly the glucose-6-phosphate dehydrogenase which was the main NADPH generating system in breast cancer cells. The present study thus suggests that BCFA synthetically lowers the fatty acid biosynthesis by reducing the precursors, in addition to its direct inhibitory effect on fatty acid synthetase.
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PMID:Effect of branched-chain fatty acids on fatty acid biosynthesis of human breast cancer cells. 1524 18

Redox signals generated by the photosynthetic electron transport chain are known to be involved in regulating the Calvin cycle, ATP synthesis, and NADPH export from chloroplasts in response to light. The signal cascade involves transfer of electrons from photosystem I via the ferredoxin-thioredoxin system to target enzymes that are activated by reduction of regulatory disulphide bonds. The purpose of this review is to discuss recent findings showing that this concept can be extended to the regulation of carbon storage and partitioning in plants. Starch is the major carbon store in plants, and ADP-glucose pyrophosphorylase (AGPase) is the key regulatory enzyme of starch synthesis in the plastid. It has been shown that AGPase from potato tubers is subject to post-translational redox modification, and here experimental data will be provided showing that the isozyme from pea leaf chloroplasts is activated by reduced thioredoxin f or m in a similar way. Recent reports will be summarized providing in planta evidence that this mechanism regulates storage starch synthesis in response to light and sugars. Post-translational redox activation of AGPase in response to sugars is part of a signalling mechanism linking the rate of starch synthesis to the availability of carbon in diverse plant tissues. Some of the components of the signalling pathway reporting changes in the cytosolic sugar status to the plastid have been postulated, but detailed work is in progress to confirm the exact mode of action. Recent evidence will be discussed showing that key enzymes of de novo fatty acid synthesis (acetyl-CoA carboxylase) and ammonium assimilation (glutamine synthetase and glutamine:oxoglutarate amino transferase) are regulated by reversible disulphide-bond formation similar to AGPase. Redox regulation is proposed to be the preferred strategy of plastidial enzymes to regulate various metabolic processes such as carbon fixation, starch metabolism, lipid synthesis, and amino acid synthesis in response to physiological and environmental inputs.
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PMID:Redox regulation of carbon storage and partitioning in response to light and sugars. 1586 46

Leucoplasts were isolated from the endosperm of developing castor (Ricinis communis) endosperm using a discontinuous Percoll gradient. The rate of fatty acid synthesis was highest when malate was the precursor, at 155 nanomoles acetyl-CoA equivalents per milligram protein per hour. Pyruvate and acetate also were precursors of fatty acid synthesis, but the rates were approximately 4.5 and 120 times less, respectively, than when malate was the precursor. When acetate was supplied to leucoplasts, exogenous ATP, NADH, and NADPH were required to obtain maximal rates of fatty acid synthesis. In contrast, the incorporation of malate and pyruvate into fatty acids did not require a supply of exogenous reductant. Further, the incorporation of radiolabel into fatty acids by leucoplasts supplied with radiolabeled malate, pyruvate, or acetate was reduced upon coincubation with cold pyruvate or malate. The data suggest that malate and pyruvate may be good in vivo sources of carbon for fatty acid synthesis and that, in these preparations, leucoplast fatty acid synthesis may be limited by activity at or downstream of the acetyl-CoA carboxylase reaction.
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PMID:Malate- and pyruvate-dependent Fatty Acid synthesis in leucoplasts from developing castor endosperm. 1666 81

Twenty-four lambs (Ovis aries) were used in a 45-day finishing study to evaluate the effects of feeding diets high in linoleic acid (C(18:2), omega-6) on liver lipid composition and on lipogenic enzyme activities in subcellular fractions of liver. Lambs were fed either a 5% safflower oil (SO, high linoleic acid) supplemented diet or a control diet without added oil. SO feeding caused a reduction in the amount of serum and liver triacylglycerols and cholesterol, whereas the level of phospholipids in both tissues was hardly affected. In liver of SO-treated lambs an increase in the levels of C(18:2) and arachidonic acid (C(20:4), omega-6), together with a simultaneous decrease of saturated fatty acids, was observed. In comparison to rat liver, rather low activities of enzymes in the pathway for de novo fatty acid synthesis, i.e. acetyl-CoA carboxylase and fatty acid synthase, were found in lamb-liver cytosol. Both enzyme activities, as well as those of the NADPH-furnishing enzymes, were significantly reduced by SO feeding. In contrast, microsomal and especially mitochondrial fatty acid chain elongation activity, the latter being much higher than that of rat liver, were significantly increased in SO-treated lambs. In these animals, a stimulation of triangle up(9)-desaturase activity was observed in liver microsomes.
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PMID:Changes in lipid composition and lipogenic enzyme activities in liver of lambs fed omega-6 polyunsaturated fatty acids. 1746 55


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