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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)

1. In the rat, acetyl-CoA carboxylase (ACC), a rate-limiting enzyme in fatty acid metabolism, exists as at least two different isozymes (M(r) 265,000 and 280,000) that display distinct tissue-specific distribution and regulation. 2. Based on the study of human tissue and human-derived breast cancer cell lines by enzyme isolation and protein blotting techniques, we have now identified two human isoforms of M(r) 265,000 (HACC 265) and 275,000 (HACC 275), each of which is homologous to one of the rat isozymes. 3. Human breast carcinoma cell lines show variable expression of these two isoforms, mirrored in the estimation of ACC acetyl-CoA kinetics.
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PMID:Identification of human acetyl-CoA carboxylase isozymes in tissue and in breast cancer cells. 791 7

Spiramycin biosynthesis in Streptomyces ambofaciens was stimulated in the presence of valine or by sequential addition of some short-chain fatty acids to a culture medium containing an ammonium salt as source of nitrogen. Acetate kinase and acetyl-CoA carboxylase, enzymes that catalysed the formation of precursors of spiramycin biosynthesis (acetyl-CoA and malonyl-CoA), were detected during the active growth and antibiotic production phases. In this latter phase a higher level of acetyl-CoA carboxylase activity was observed with valine (1.02 mumol.min-1.mg protein-1) than with ammonium (0.05 mumol.min-1.mg protein-1) as nitrogen source, while the evolution and the level of acetate kinase activity were the same in both media. Successive addition of acetate and isobutyrate stimulated highly and weakly the acetyl-CoA carboxylase and acetate kinase activity, respectively.
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PMID:Relationship between valine, fatty acids, and spiramycin biosynthesis in Streptomyces ambofaciens. 792 89

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

Steady-state kinetics of the 220-kDa form of acetyl-CoA carboxylase (ACC220), as purified from mature pea seeds, have been investigated with respect to the substrate specificity and inhibition by quizalofop, a herbicide of the aryloxyphenoxypropionate type. The enzyme showed a dual specificity, being able to carboxylate propionyl-CoA at a maximal rate approximately 20% that measured in the presence of the acetyl-CoA substrate. These two reactions occur at separate sites on the enzyme. One site binds either acetyl-CoA (Km = 226 microM) or propionyl-CoA (Km = 38 microM) and is strongly inhibited by quizalofop (Ki = 25 microM and 9.3 microM for the acetyl-CoA and propionyl-CoA substrates, respectively). The other is specific for acetyl-CoA (Km = 11 microM) and is much less inhibited by quizalofop (Ki = 256 microM). Owing to the existence of these two catalytically different sites, the enzyme obeyed Michaelis-Menten kinetics with propionyl-CoA, but exhibited kinetic co-operativity in the presence of acetyl-CoA. Also, kinetics of propionyl-CoA carboxylase activity of ACC220 exhibited hyperbolic inhibition in the presence of quizalofop, but co-operative inhibition when following the ACC activity of the enzyme. The results suggest that the higher the substrate specificity, the lower the quizalofop sensitivity of the active site. Similar kinetic behaviour was observed with ACC220 purified from pea leaves. Also, the apparent correlation between the substrate specificity and the sensitivity of ACC towards quizalofop was confirmed by kinetic analyses of the low-molecular-mass form of ACC present in chloroplasts of young pea leaves. This enzyme was insensitive to quizalofop inhibition and was not able to carboxylate propionyl-CoA. No other propionyl-CoA carboxylase activity, different from that catalysed by ACC220, could be detected from either reproductive or vegetative organs of pea plants at any stage of development.
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PMID:Kinetics of the two forms of acetyl-CoA carboxylase from Pisum sativum. Correlation of the substrate specificity of the enzymes and sensitivity towards aryloxyphenoxypropionate herbicides. 795 2

A fatty acid chain elongation process is involved in incorporation of saturated and unsaturated fatty acyl-CoA esters into 2-tridecanone and (Z)-10-heptadecen-2-one by Drosophila buzzatii. The microsomal fraction from mature male ejaculatory bulbs is chain-length specific and requires malonyl-CoA (or acetyl-CoA, if acetyl-CoA carboxylase were present) for the chain elongation step to 2-ketones. Decarboxylation of the proposed intermediate beta-ketoacid results in 2-ketone biosynthesis. Incubation of the microsomes with the acetyl-CoA carboxylase inhibitor avidin indicated that acetyl-CoA carboxylase was present in the microsomal preparations; however, washing of the microsomal preparation removed the acetyl-CoA carboxylase activity. Fatty acyl-CoA esters were also chain elongated to produce fatty acids two and four carbons longer, suggesting that the enzymes for normal fatty acid chain elongation are also present in the microsomal fraction from ejaculatory bulbs. How much, if any, of this fatty acid chain elongation system is used for 2-ketone biosynthesis is yet to be determined.
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PMID:Fatty acid elongation in the biosynthesis of (Z)-10-heptadecen-2-one and 2-tridecanone in ejaculatory bulb microsomes of Drosophila buzzatii. 798 31

Sulfur-substituted fatty acid analogues have been administered to rats fed a high carbohydrate diet, and the effect on plasma and hepatic lipid metabolism was investigated. Two of the analogues studied, 3-thiadicarboxylic acid and tetradecylthioacetic acid, reduced the plasma cholesterol level significantly, whereas the effect on plasma triacylglycerol level was only marginal. 3-Thiadicarboxylic acid was the most potent, decreasing the cholesterol level faster and at a lower dose than tetradecylthioacetic acid. The relative effects on plasma cholesterol and triacylglycerol levels were different from what have been observed in rats fed a conventional pellet diet. Tetradecylthiopropionic acid had no hypocholesterolemic effect. The activities of three lipogenic enzymes: ATP-citrate lyase, acetyl-CoA carboxylase and fatty acid synthase was measured. The two hypocholesterolemic analogues reduced the activities of these enzymes in a coordinated manner. The enzyme activities was found to correlate with the the plasma cholesterol level, indicating a coordinated regulation of these enzymes and cholesterol synthesis or secretion. The effect on two enzymes involved in cholesterol metabolism was also studied. The activity of acyl-CoA:cholesterol acyltransferase (ACAT) was reduced by the two hypocholesterolemic analogues, in contrast to the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, which tended to increase. The cholesterol lowering effect of 3-thiadicarboxylic acid and tetradecylthioacetic acid can probably be ascribed to diminished cholesterol synthesis due to a reduced availability of acetyl-CoA. A reduction in the esterification of hepatic cholesterol may be a contributing factor.
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PMID:The hypocholesterolemic effect of sulfur-substituted fatty acid analogues in rats fed a high carbohydrate diet. 846 46

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

Fatty acids in fish can arise from two sources: synthesis de novo from non-lipid carbon sources within the animal, or directly from dietary lipid. Acetyl-CoA derived mainly from protein can be converted to saturated fatty acids via the combined action of acetyl-CoA carboxylase and fatty acid synthetase. The actual rate of fatty acid synthesis de novo is inversely related to the level of lipid in the diet. Freshwater fish can desaturate endogenously-synthesized fatty acids to monounsaturated fatty acids via a delta 9 desaturase but lack the necessary enzymes for complete de novo synthesis of polyunsaturated fatty acids which must therefore be obtained preformed from the diet. Most freshwater fish species can desaturate and elongate 18:2(n-6) and 18:3(n-3) to their C20 and C22 homologues but the pathways involved remain ill-defined. Cyclooxygenase and lipoxygenase enzymes can convert C20 polyunsaturated fatty acids to a variety of eicosanoid products. The dietary ratio of (n-3) to (n-6) polyunsaturated fatty acids influences the pattern of eicosanoids formed. The beta-oxidation of fatty acids can occur in both mitochondria and peroxisomes but mitochondrial beta-oxidation is quantitatively more important and can utilise a wide range of fatty acid substrates.
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PMID:Fatty acid metabolism in freshwater fish with particular reference to polyunsaturated fatty acids. 876 69

The steady-state kinetics of two multifunctional isoforms of acetyl-CoA carboxylase (ACCase) from maize leaves (a major isoform, ACCase1 and a minor isoform, ACCase2) have been investigated with respect to reaction mechanism, inhibition by two graminicides of the aryloxyphenoxypropionate class (quizalofop and fluazifop) and some cellular metabolites. Substrate interaction and product inhibition patterns indicated that ADP and P(i) products from the first partial reaction were not released before acetyl-CoA bound to the enzymes. Product inhibition patterns did not match exactly those predicted for an ordered Ter Ter or a random Ter Ter mechanism, but were close to those postulated for an ordered mechanism. ACCase2 was about 1/2000 as sensitive as ACCase1 to quizalofop but only about 1/150 as sensitive to fluazifop. Fitting inhibition data to the Hill equation indicated that binding of quizalofop or fluazifop to ACCase1 was non-cooperative, as shown by the Hill constant (n(app)) values of 0.86 and 1.16 for quizalofop and fluazifop respectively. Apparent inhibition constant values (K' from the Hill equation) for ACCase1 were 0.054 microM for quizalofop and 21.8 microM for fluazifop. On the other hand, binding of quizalofop or fluazifop to ACCase2 exhibited positive co-operativity, as shown by the (napp) values of 1.85 and 1.59 for quizalofop and fluazifop respectively. K' values for ACCase2 were 1.7 mM for quizalofop and 140 mM for fluazifop. Kinetic parameters for the co-operative binding of quizalofop to maize ACCase2 were close to those of another multifunctional ACCase of limited sensitivity to graminicide, ACC220 from pea. Inhibition of ACCase1 by quizalofop was mixed-type with respect to acetyl-CoA or ATP, but the concentration of acetyl-CoA had the greater effect on the level of inhibition. Neither ACCase1 nor ACCase2 was appreciably sensitive to CoA esters of palmitic acid (16:0) or oleic acid (18:1). Approximate IC50 values were 10 microM (ACCase2) and 50 microM (ACCase1) for both CoA esters. Citrate concentrations up to 1 mM had no effect on ACCase1 activity. Above this concentration, citrate was inhibitory. ACCase2 activity was slightly stimulated by citrate over a broad concentration range (0.25-10 mM). The significance of possible effects of acyl-CoAs or citrate in vivo is discussed.
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PMID:Kinetic studies on two isoforms of acetyl-CoA carboxylase from maize leaves. 883 49

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


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