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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)

We have isolated and determined the nucleotide sequence of the yeast FAS3 gene, which encodes acetyl-CoA carboxylase (EC 6.4.1.2). The sequence has an open reading frame of 6711 bases coding for a protein of 2237 amino acids with a calculated molecular weight of 250,593. The presence of the unique biotin-binding site, Met-Lys-Met, and the known CNBr peptide and COOH-terminal sequences confirmed the nucleotide-derived amino acid sequence. The yeast, chicken, and rat carboxylases have an overall sequence identity of 34%, suggesting that the eukaryotic carboxylase evolved from a single ancestral gene. The amino acid sequences of yeast fatty acid synthase subunits are least homologous with the animal synthase sequences, whereas carboxylase sequences are highly conserved. The sequences of the ATP, HCO3-, and CoA binding sites of the carboxylases are also well conserved (approximately 50% identical). The sequences surrounding the biotin binding site are poorly conserved, suggesting that this sequence may not be critical as long as the biotin is available for carboxylase reactions. On the basis of this sequence identity, we have defined the putative biotin carboxylase and transcarboxylase domains.
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PMID:Cloning of the yeast FAS3 gene and primary structure of yeast acetyl-CoA carboxylase. 135 93

The interaction of rat liver acetyl-CoA carboxylase with a 2',3'-dialdehyde derivative of ATP (oATP) has been studied. The degree of the enzyme inactivation has been found to depend on the oATP concentration and the incubation time. ATP was proved to be the only substrate which protected the inactivation. Acetyl-CoA did not effect inactivation, while HCO3- accelerated the process. Ki values for oATP in the absence and presence of HCO3- were 0.35 +/- 0.04 and 0.5 +/- 0.06 mM, and those of the modification constant (kmod) were 0.11 and 0.26 min-1 respectively. oATP completely inhibited the [14C]ADP in equilibrium ATP exchange and did not effect the [14C]acetyl-CoA in equilibrium malonyl-CoA exchange. Incorporation of approximately 1 equivalent of [3H]oATP per acetyl-CoA carboxylase subunit has been shown. No recovery of the modified enzyme activity has been observed in Tris or beta-mercaptoethanol containing buffers, and treatment with NaB3H4 has not led to 3H incorporation. The modification elimination of the ATP triphosphate chain. The results indicated the affinity modification of acetyl-CoA carboxylase by oATP. It was shown that the reagent apparently interacted selectively with the epsilon-amino group of lysine in the ATP-binding site to form a morpholine-like structure.
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PMID:Affinity labelling of rat liver acetyl-CoA carboxylase by a 2',3'-dialdehyde derivative of ATP. 196 47

The interaction of rat liver acetyl-CoA carboxylase with a 2',3'-dialdehyde derivative of ATP (oATP) has been studied. The degree of the enzyme inactivation has been found to depend on the oATP concentration and the incubation time. ATP was the only reaction substrate which provided protection from inactivation. Acetyl-CoA did not affect inactivation, while HCO3- accelerated the process. Ki values for oATP in the absence and the presence of HCO3- were 0.35 +/- 0.04 and 0.5 +/- 0.06 mM, and those of the modification constant (k) were 0.11 and 0.26 min-1, respectively. oATP completely inhibited the reaction of [14C]ADP in equilibrium ATP exchange, whereas produced actually no effect on [14C]acetyl-CoA equilibrium with malonyl-CoA exchange. Incorporation of about one equivalent of [3H]oATP per acetyl-CoA carboxylase subunit has been shown. No restoration of the modified enzyme activity has been observed in Tris or beta-mercaptoethanol containing buffers, and treatment with NaB[3H]4 has not led to 3H incorporation. The modification process involves elimination of the triphosphate chain of oATP. The results obtained indicate the affinity character of oATP-mediated modification of acetyl-CoA carboxylase. The reagent apparently interacts selectively with the epsilon-amino group of lysine in the ATP-binding site to form a morpholine-like structure.
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PMID:[Acetyl-CoA-carboxylase: modification of ATP-binding site of the active center by 2',3'-dialdehyde derivative of ATP]. 257 82

The kinetic time course of citrate-induced activation and polymerization (into filaments) of the protomeric form of acetyl-CoA carboxylase were compared to assess the concertedness of the two processes. Rapid-quench techniques were employed to measure the kinetics of activation of the carboxylase-catalyzed reaction by citrate. When enzyme was preincubated with citrate prior to initiating the steady state turnover reaction with acetyl-CoA in the rapid-quench device, the observed rate of carboxylation of acetyl-CoA was apparently linear from the moment of mixing. However, when enzyme was mixed with citrate to initiate the reaction, a lag (t1/2 = 0.7 s) occurred in the approach to steady state carboxylation rate. This lag was independent of enzyme concentration over a 230-fold range and was marginally dependent upon citrate concentration. Over the same range of enzyme concentration, polymerization of carboxylase protomers, as determined by right angle light scattering, was enzyme concentration-dependent in a manner predicted by a single protomer activation step, followed by a rate-limiting dimerization of active protomer and subsequent polymerization. Polymerization is a second order process, with a second order rate constant of 597,000 M-1 s-1. There appear to be two steps that limit polymerization of the inactive carboxylase protomer: a rapid citrate-induced conformational change, which is independent of enzyme concentration and leads to an active protomeric form of the enzyme and the dimerization of the active protomer, which constitutes the first step of polymerization and is enzyme concentration-dependent. Dimerization is the rate-limiting step of acetyl-CoA carboxylase polymerization. On the basis these results, it is concluded that activation of catalysis and the polymerization of carboxylase protomers are not concerted. Furthermore, activation of carboxylation leading to the formation of an active protomer was faster than polymerization under all conditions, and therefore precedes polymerization. It was also shown that the activation constant (Kact) for citrate is altered in a predictable manner by the accumulation of the reaction product, malonyl-CoA, the Kact increasing with malonyl-CoA concentration. Depolymerization of fully polymerized acetyl-CoA carboxylase is caused by malonyl-CoA or ATP.Mg (and HCO3-). Both malonyl-CoA and ATP.Mg (and HCO3-) compete with citrate in the maintenance of a given state of the protomer-polymer equilibrium apparently by carboxylating the enzyme to form enzyme-biotin CO2- which destabilizes the polymeric form.
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PMID:Kinetics of citrate-induced activation and polymerization of chick liver acetyl-CoA carboxylase. 286 79

In a previous study (A. ENDO, et al., J. Antibiotics 38: 599 approximately 604, 1985), 2-alkyl glutarate and its derivatives isolated from cultures of Gongronella butleri were shown to inhibit animal acetyl-CoA carboxylase. In the present communication, the inhibition of liver acetyl-CoA carboxylase was investigated with several 2-alkyl glutarate and 2-alkyl succinate analogs. Their inhibitory potency increased with the chain length of the alkyl moiety, and 2-tetradecanylglutarate was most potent among the inhibitors tested. Kinetic analysis indicated that inhibition by 2-tetradecanylglutarate was non-competitive with respect to the substrates, ATP, HCO3- and acetyl-CoA, and competitive with respect to the allosteric regulatory citrate, giving a Ki value of 40 microM. Sucrose density gradient centrifugation analysis showed that the citrate-induced polymerization of the enzyme was inhibited by 2-tetradecanylglutarate.
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PMID:Inhibition of liver acetyl-coenzyme-A carboxylase by 2-tetradecanylglutarate. 287 47

A wild-type Streptomyces strain, yielding 1 g/L of oxytetracycline was compared with mutants giving up to 7 g/L, using complex media in stirred and shaken culture. Increased production of oxytetracycline was associated with high specific production rates and a longer production period. The superiority of the mutants was associated with changes in morphological behaviour during growth in submerged culture, and in their patterns of growth and respiration, coupled with increased resistance to the product. The productivity of the mutants was sensitive to the rate of stirring, the type of calcium carbonate used in the medium and the type of inoculum. Careful control of these factors was necessary to obtain high yields of oxytetracycline. With the exception of acetyl-CoA carboxylase, the levels of enzymes measured and of amounts of adenylates in the mycelium did not appear to be related to the degree of antibiotic production.
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PMID:Physiology of a wild strain and high yielding mutants of Streptomyces rimosus, producing oxytetracycline. 289 94

The interaction of 4-(N-chloroethyl-N-methylamino)-benzyl-gamma-amide ATP (I) and the corresponding beta-amide of ADP (II) with rat liver acetyl-CoA carboxylase was studied. Both analogs were shown to cause affinity modification of the enzyme. ATP and GoAS Ac protected the enzyme against inactivation. HCO3- increased the rate of carboxylase inactivation by analogs I and II (2.5- and 1.5-fold, respectively). The alkylating amides did not influence the rate of the bicarbonate-dependent [14C]-ADP-ATP exchange and inhibited the enzyme-catalyzed reaction of [14C]-CoAs Ac----CoAS Mal exchange, which testifies to the localization of the modified group in the CoAS Ac-binding site of the enzyme active center. Based on the affinity modification and analog size, it was found that the distance between the ATP- and CoAS Ac-binding sites of the enzyme active center can vary from 0.8 to 1.2 nm.
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PMID:[Interaction of acetyl-CoA-carboxylase from the rat liver with alkylating amides of ATP and ADP]. 290 6

Avidin affinity chromatography was used to rapidly purify acetyl-CoA carboxylase to homogeneity in high yield from chicken liver. Dissociation of the purified carboxylase with dodecyl sulfate yielded a single size class of subunit polypeptide of 225,000 daltons. A steady state kinetic analysis of the carboxylase-catalyzed carboxylation of acetyl-CoA gave rise to intersecting line patterns in all double-reciprocal plots of initial velocity with each substrate pair, i.e. ATP . Mg and HCO3(-) and acetyl-CoA. It was concluded that the kinetic mechanism involves a quaternary complex of the enzyme, ADP, Pi, and acetyl-CoA rather than a double displacement as previously believed. The ordered addition of ATP, HCO3(-), and then acetyl-CoA, to the citrate-activated form of the carboxylase is the kinetic mechanism most consistent with the results.
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PMID:Acetyl coenzyme A carboxylase. Rapid purification of the chick liver enzyme and steady state kinetic analysis of the carboxylase-catalyzed reaction. 611 14

A kinetic analysis of the activity of acetyl-CoA carboxylase from chicken liver upon alimentary activation of lipogenesis and inhibition of this reaction by nicotinic acid was performed. It was found that the affinity of the enzyme isolated from chicken liver with stimulated lipogenesis is decreased by nicotinic acid for HCO3- but remains unchanged for ATP. The value of Vmax for ATP and the amount of the ATP used in this reaction remain unaffected. At the same time the enzyme affinity for acetyl-CoA is increased with a simultaneous decrease of Vmax. It is assumed that nicotinic acid inhibits the first step of the acetyl-CoA carboxylase-catalyzed reaction.
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PMID:[Mechanism of nicotinic acid inhibition of the reaction catalyzed by acetyl-CoA carboxylase]. 613 54

Maize leaf acetyl-CoA carboxylase was purified from whole tissue homogenates by precipitation with polyethylene glycol and ammonium sulfate, and gel filtration. Recoveries were approximately 5% with 100-fold increases in specific activity. The molecular weight of the native enzyme is estimated at 500,000 from the elution volume of a calibrated Ultrogel AcA 22 column. Electrophoresis in polyacrylamide gel containing 1% sodium dodecyl sulfate revealed a single subunit of Mr 60,000-61,000. Investigation of the kinetic properties of the purified enzyme indicates that Mg X ATP is the active substrate, with free ATP inhibiting and Mg2+ activating the enzyme. Km's for acetyl-CoA and HCO3- are about 0.1 and 2 mM, respectively. ADP inhibition is competitive with respect to ATP, but uncompetitive with respect to acetyl-CoA. The observed responses of purified acetyl-CoA carboxylase to changes in pH, and in concentrations of Mg2+, ATP, and ADP, and the reported changes in the chloroplastic concentrations of these effectors during light-dark transitions of chloroplasts are consistent with increased acetyl-CoA carboxylase activity upon illumination of chloroplasts.
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PMID:Purification and characterization of maize leaf acetyl-coenzyme A carboxylase. 614 67


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