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)

The possibility of biosynthesis of cholic (I) and chenodeoxycholic (II) acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in a reconstituted system of rat liver and the incorporation of acetyl-CoA into these bile acids under conditions of acetyl-CoA carboxylase activation by citrate or its inhibition by avidin were studied. The effects of Triton WR 1339 and cholesterol feeding on acetyl-CoA and malonyl-CoA incorporation into I and II were investigated. Teh incorporation of both substrates into the total unsaponifiable lipid fraction and fatty acids was demonstrated. The reconstituted system of rat liver was found able to synthesize and I and II not only from acetyl-CoA, but from malonyl-CoA as well. The rate of malonyl-CoA incorporation into the bile acids was somewhat higher than that of acetyl-CoA incorporation. Preincubation of the reconstituted system with citrate stimulated the rate of acetyl-CoA incorporation into I. Stimulation of biosynthesis of I occurred independently of the diurnal rhythm of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) activity. An addition of avidin to the reconstituted system preincubated with citrate caused inhibition of acetyl-CoA incorporation both into fatty acids and into I. The rate of biosynthesis of II remained practically unchanged in both cases. Treatment with Triton WR 1339 had only a slight effect, while cholesterol feeding significantly stimulated the incorporation of acetyl-CoA and malonyl-CoA into I and II. The results obtained suggest the participation of malonyl-CoA in formation of bile acids, preferentially cholic acid, and in a lesser degree, in sterol biosynthesis. Data from stimulation of bile acid biosynthesis under cholesterol feeding suggest that HMG-CoA reductase localized in the soluble fraction of rat liver is involved in bile acid biosynthesis.
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PMID:[Biosynthesis of cholic and chenodeoxycholic acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in a reconstituted system from the rat liver]. 723 4

Rates of fatty acid synthesis from lactate and acetate and activities of selected lipogenic and NADPH-generating enzymes were determined in subcutaneous, intermuscular and intramuscular adipose tissues of cattle that were 11-19 months of age. Fatty acid synthesis from lactate and acetate increased from 11 to 13 months of age in subcutaneous and intermuscular adipose tissues; synthesis from lactate increased until 17 months of age. In intramuscular adipose tissue, synthesis from lactate also increased until 17 months of age while that from acetate continually increased. Activities of NADPH-generating enzymes increased in all three fat depots from 11 to 13 months of age, and little change occurred thereafter. Acetyl-CoA carboxylase activity was constant over entire growth period in all depots. Activity of ATP-citrate lyase increased from 11 to 13 months of age in subcutaneous and intermuscular adipose tissues, but did not increase until 19 months of age in intramuscular adipose tissue. In all cases, activities of ATP-citrate lyase were sufficient to support synthesis from lactate; therefore, lactate conversion to fatty acids in bovine adipose tissues seems to use the citrate cleavage pathway for generation of cytosolic acetyl-CoA.
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PMID:Fatty acid synthesis from lactate in growing cattle. 726 74

Acetyl-CoA carboxylase [ACCase; acetyl-CoA:carbon dioxide ligase (ADP forming), EC 6.4.1.2] catalyses the ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA. We have amplified a fragment of the biotin carboxylase (BC) domain of the Ustilago maydis acetyl-CoA carboxylase (ACC1) gene from genomic DNA and used this amplified DNA fragment as a probe to recover the complete gene from a lambda EMBL3 genomic library. The ACC1 gene has a reading frame of 6555 nucleotides, which is interrupted by a single intron of 80 bp in length. The gene encodes a protein containing 2185 amino acids, with a calculated M(r) of 242,530; this is in good agreement with the size of ACCases from other sources. Further identification was based on the position of putative binding sites for acetyl-CoA, ATP, biotin and carboxybiotin found in other ACCases. A single ACC1 allele was disrupted in a diploid wild-type strain. After sporulation of diploid disruptants, no haploid progeny containing a disrupted acc1 allele were recovered, even though an exogenous source of fatty acids was provided. The data indicate that, in U. maydis, ACCase is required for essential cellular processes other than de novo fatty acid biosynthesis.
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PMID:The ACC1 gene, encoding acetyl-CoA carboxylase, is essential for growth in Ustilago maydis. 750 Sep 41

Acetyl-CoA carboxylase (ACCase) catalyzes the carboxylation of acetyl-CoA, forming malonyl-CoA a key intermediate in the biosynthesis of fatty acids and a variety of secondary metabolites. Based upon amino acid sequences conserved among rat, chicken, and E. coli ACCases, PCR-primers were used to amplify a genomic fragment which codes for an ACCase of Arabidopsis. The resulting fragment was used for isolation of genomic and cDNA clones. We have determined the complete cDNA sequence coding for an Arabidopsis ACCase consists of 2,254 amino acids with the molecular mass of 251 kDa. This enzyme contains no recognizable plastid transit-peptide sequence. Therefore, this ACCase is presumably the cytosolic isozyme. Southern analysis indicates that there are two ACCase genes in the Arabidopsis genome. Surprisingly, the results of RFLP analysis and physical mapping of the isolated genomic clones demonstrate that these two genes, acc1 and acc2, are contiguously located within a 25-kbp genomic region near the middle of chromosome 1. Both genes are transcriptionally active, as transcripts from each gene were detected by reverse transcription-PCR analysis using gene-specific primers. The acc1 and acc2 transcripts accumulate in leaves and seedlings but only the acc1 transcript accumulates in developing siliques, unexpectedly. The differences in the expression patterns may be indicative of the differential role of the two genes.
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PMID:Genomic organization of 251 kDa acetyl-CoA carboxylase genes in Arabidopsis: tandem gene duplication has made two differentially expressed isozymes. 755 84

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

The enzyme activities responsible for carboxylation reactions in cell extracts of the gastric pathogen Helicobacter pylori have been studied by H14CO3- fixation and spectrophotometric assays. Acetyl coenzyme A carboxylase (EC 6.4.1.2) and malic enzyme (EC 1.1.1.40) activities were detected, whereas pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxylase (EC 4.1.3.1) and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) activities were absent. However, a pyruvate-dependent, ATP-independent, and avidin-insensitive H14CO3- fixation activity, which was shown to be due to the isotope exchange reaction of pyruvate:flavodoxin oxidoreductase (EC 1.2.7.1), was present. The purified enzyme is composed of four subunits of 47, 36, 24, and 14 kDa. N-terminal sequence analysis showed that this enzyme is related to a recently recognized group of four-subunit pyruvate:ferredoxin oxidoreductases previously known only from hyperthermophiles. This enzyme from H. pylori was found to mediate the reduction of a number of artificial electron acceptors in addition to a flavodoxin isolated from H. pylori extracts, which is likely to be the in vivo electron acceptor. Indirect evidence that the enzyme is capable of in vitro reduction of the anti-H. pylori drug metronidazole was also obtained.
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PMID:Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate:flavodoxin oxidoreductase from Helicobacter pylori. 760 66

An acetyl-CoA carboxylase has been purified from rat hindlimb muscle using ammonium sulfate fractionation and avidin-Sepharose affinity chromatography. SDS/PAGE of the isolated enzyme showed a major protein band at approximately 272 kDa and a minor band at 265 kDa. The liver acetyl-CoA carboxylase gave a major protein band at 265 kDa and a minor band at 280 kDa. Adipose tissue acetyl-CoA carboxylase migrated to the 265-kDa position on the gel. Western blots performed using streptavidin-alkaline-phosphatase suggest that the bands from the three tissues contain biotin. The present study has characterized the muscle and adipose tissue enzymes under steady-state kinetics and determined Michaelis constants for the substrates. The activation constant for citrate, an essential activator for both preparations, was 2.13 +/- 0.05 mM for the muscle enzyme and 3.02 +/- 0.12 mM for adipose tissue (P < 0.01). The Km values for the muscle acetyl-CoA carboxylase compared to the adipose tissue acetyl-CoA carboxylase were: ATP, 57.6 +/- 0.9 microM compared to 106.5 +/- 2.6 microM, P < 0.01; acetyl-CoA, 31.7 +/- 1.5 microM compared to 21.5 +/- 1.0 microM, P < 0.01; bicarbonate, 2.25 +/- 0.10 mM compared to 2.73 +/- 0.29 mM, P > 0.05. The muscle acetyl-CoA carboxylase was inhibited by malonyl-CoA (Ki = 10.6 +/- 1.0 microM) and palmitoyl-CoA (Ki = 2.2 +/- 0.3 microM). These properties are consistent with the hypothesis that regulation of acetyl-CoA carboxylase plays an important role in governing the rate of fatty acid oxidation in the skeletal muscle.
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PMID:Purification and characterization of rat skeletal muscle acetyl-CoA carboxylase. 762 70

Acetyl coenzyme A (CoA) carboxylase catalyzes the synthesis of malonyl-CoA, the first intermediate of fatty acid synthesis. The Escherichia coli enzyme is encoded by four subunits located at three different positions on the E. coli chromosome. The accBC genes lie in a small operon at min 72, whereas accA and accD are located at min 4.3 and 50, respectively. We examined the expression of the genes that encode the E. coli acetyl-CoA carboxylase subunits (accA, accBC, and accD) under a variety of growth conditions by quantitative Northern (RNA) blot analysis. We found a direct correlation between the levels of transcription of the acc genes and the rate of cellular growth. Consistent results were also obtained upon nutritional upshift and downshift experiments and upon dilution of stationary-phase cultures into fresh media. We also determined the 5' end of the accA and accD mRNAs by primer extension and did transcriptional fusion analysis of the previously reported accBC promoter. Several interesting features were found in the promoter regions of these genes, including a bent DNA sequence and an open reading frame within the unusually long leader mRNA of the accBC operon, potential stem-loop structures in the accA and accD mRNA leader regions, and a stretch of GC-rich sequences followed by AT-rich sequences common to all three promoters. In addition, both accA and accD are located in complex gene clusters. For example, the accA promoter was localized within the upstream polC gene (which encodes the DNA polymerase III catalytic subunit), suggesting that additional regulatory mechanisms exist.
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PMID:Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzes the first committed step of lipid biosynthesis. 767 42

It has long been known that most of the energy production in the heart is derived from the oxidation of fatty acids. The other important sources of energy are the oxidation of carbohydrates and, to a lesser extent, ATP production from glycolysis. The contribution of these pathways to overall ATP production can vary dramatically, depending to a large extent on the carbon substrate profile delivered to the heart, as well as the presence or absence of underlying pathology within the myocardium. Despite extensive research devoted to the study of the individual pathways of energy substrate metabolism, relatively few studies have examined the integrated regulation between carbohydrate and fatty acid oxidation in the heart. While the mechanisms by which fatty acids inhibit carbohydrate oxidation (i.e., the Randle cycle) have been characterized, much less is known about how carbohydrates regulate fatty acid oxidation in the heart. It is clear that an increase in intramitochondrial acetyl-CoA derived from carbohydrate oxidation (via the pyruvate dehydrogenase complex) can downregulate beta-oxidation of fatty acids, but it is not clear how fatty acid acyl group entry into the mitochondria is downregulated when carbohydrate oxidation increases. Recent interest in our laboratory has focused on the involvement of acetyl-CoA carboxylase (ACC) in this process. While it has been known for some time that malonyl-CoA does exist in heart tissue, and that it is a potent inhibitor of carnitine palmitoyltransferase 1 (CPT 1), it has only recently been demonstrated that an isoenzyme of ACC exists in the heart that is a potential source of malonyl-CoA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1993 Merck Frosst Award. Acetyl-CoA carboxylase: an important regulator of fatty acid oxidation in the heart. 788 73

Acetyl-CoA carboxylase is the rate-limiting enzyme in the biogenesis of long-chain fatty acids. In order to understand the mechanisms that regulate human acetyl-CoA carboxylase at the gene level, and the relationship between its structure and function, cDNA clones for human acetyl-CoA carboxylase have been isolated and sequenced. Human acetyl-CoA-carboxylase cDNA contains 7020 nucleotides encoding a protein of 2340 amino acids with a calculated relative molecular mass of 264575. The human enzyme shows approximately 85% identity in nucleotide sequence with previously cloned rat acetyl-CoA carboxylase, and shows 90% identity in the amino acid sequence. Two human acetyl-CoA-carboxylase mRNA species, which differ in the 5' untranslated region with the same coding sequence, have been identified. The sequence analysis reveals that type I and type II acetyl-CoA-carboxylase mRNA contain 313- and 173-base-long 5' untranslated regions, respectively. The first 240 nucleotides in the 5' untranslated region of type I acetyl-CoA-carboxylase mRNA replace the first 100 nucleotides of the (G + C)-rich region of the 5' untranslated region of the type II mRNA. These two species of mRNAs are the only species of human ACC mRNA which have been detected compared to at least five species in rat tissues, and they are expressed in a tissue-specific manner.
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PMID:Cloning of human acetyl-CoA carboxylase cDNA. 790 25


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