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)

In the plastids of most plants, acetyl-CoA carboxylase (ACCase; EC 6.4.1.2) is a multisubunit complex consisting of biotin carboxylase (BC), biotin-carboxyl carrier protien (BCCP), and carboxytransferase (alpha-CT, beta-CT) subunits. To better understand the regulation of this enzyme, we have isolated and sequenced a BC genomic clone from Arabidopsis and partially characterized its promoter. Fifteen introns were identified. The deduced amino acid sequence of the mature BC protein is highly conserved between Arabidopsis and tobacco (92.6% identity). BC expression was evaluated using northern blots and BC/GUS fusion constructs in transgenic Arabidopsis. GUS activity in the BC/GUS transgenics as well as transcript level of the native gene were both found to be higher in silique and flower than in root and leaf. Analysis of tobacco suspension cells transformed with truncated BC promoter/GUS gene fusions indicated the region from -140 to +147 contained necessary promoter elements which supported basal gene expression. A positive regulatory region was found to be located between -2100 and -140, whereas a negative element was possibly located in the first intron. In addition, several conserved regulatory elements were identified in the BC promoter. Surprisingly, although BC is a low-abundance protein, the expression of BC/GUS fusion constructs was similar to 35S/GUS constructs.
Plant Mol Biol 1997 Nov
PMID:Isolation and characterization of an Arabidopsis biotin carboxylase gene and its promoter. 934 76

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.
Exp Mol Med 1998 Jun 30
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

Transcription of the acetyl-CoA carboxylase (ACC)-alpha gene is initiated from two promoters, promoter I (PI) and promoter II (PII) such that transcripts demonstrate heterogeneity in their 5' untranslated regions (UTR). Exons 1 and 2 (E1 and E2) are the primary exons in transcripts initiated from PI and PII respectively; E5 is the first coding exon present in all transcripts. In addition alternative exon splicing results in transcripts that either include or exclude a 47 nucleotide sequence corresponding to E4, such that E[1/4/5] and E[1/5] type transcripts result from PI activity, whereas transcripts containing E[2/4/5] or E[2/5] in the 5'UTR result from PII. In subcutaneous adipose tissue from non-pregnant non-lactating sheep approximately 60% of ACC-alpha transcripts are derived from PI, of which 85% are the E[1/5] type. Lactation resulted in an 88% reduction in total PI transcripts, of which the E[1/5] type was reduced 90% and the E[1/4/5] type 80%. By contrast lactation reduced the total levels of PII transcripts by only 50%. Culture of explants from the subcutaneous depot of lactating sheep with insulin plus dexamethasone for 72 h resulted in an 8-fold increase in both E[1/4/5] and E[1/5] types when compared with explants prior to culture. PII transcripts, by contrast, were increased 2-fold by culture in insulin plus dexamethasone and this was entirely attributed to an increase in the expression of the E[2/4/5] type. Dexamethasone acts to potentiate the action of insulin on PI and PII transcript abundance and this effect is greatest for PI transcripts. This study has demonstrated that repression of the ACC-alpha gene in adipose tissue during lactation is largely achieved through attenuation of PI transcript abundance and may be related, in part, to a change in the sensitivity of the apparatus that regulates PI transcript steady-state levels to insulin.
J Mol Endocrinol 1999 Feb
PMID:Insulin-glucocorticoid interactions in the regulation of acetyl-CoA carboxylase-alpha transcript diversity in ovine adipose tissue. 992 82

In a screen for mutants that display synthetic lethal interaction with hpr1Delta, a hyperrecombination mutant of Saccharomyces cerevisiae, we have isolated a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1(cs), encoding the rate-limiting enzyme of fatty acid synthesis. The synthetic lethal phenotype of the acc1(cs) hpr1Delta double mutant was only partially complemented by exogenous fatty acids. hpr1Delta was also synthetically lethal with a previously isolated, temperature-sensitive allele of ACC1, mtr7 (mRNA transport), indicating that the lethality of the acc1(cs) hpr1Delta double mutant was not allele specific. The basis for the interaction between conditional acc1 alleles and hpr1Delta was investigated in more detail. In the hpr1Delta mutant background, acetyl-CoA carboxylase enzyme activity was reduced about 15-fold and steady-state levels of biotinylated Acc1p and ACC1 mRNA were reduced 2-fold. The reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered lipid or fatty acid composition of the mutant membranes but rendered cells hypersensitive to soraphen A, an inhibitor of Acc1p. Similar to mtr7, hpr1Delta and acc1(cs) mutant cells displayed a defect in nuclear export of polyadenylated RNA. Oversized transcripts were detected in hpr1Delta, and rRNA processing was disturbed, but pre-mRNA splicing appeared wild type. Surprisingly, the transport defect of hpr1Delta and acc1(cs) mutant cells was accompanied by an altered ring-shaped structure of the nucleolus. These observations suggest that the basis for the synthetic lethal interaction between hpr1Delta and acc1 may lie in a functional overlap of the two mutations in nuclear poly(A)+ RNA production and export that results in an altered structure of the nucleolus.
Mol Cell Biol 1999 May
PMID:The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and causes a defect in nuclear export of polyadenylated RNA. 1020 65

The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.
Mol Cell Biol 1999 May
PMID:ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. 1020 99

After in vivo administration of lead nitrate, functional changes of the mitochondrial tricarboxylate carrier and of the cytosolic lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthetase have been detected in rat liver. The rate of citrate transport was greatly reduced in rats during both the proliferative phase (3 days after the lead nitrate administration) and the involutive phase (5 days after the metal injection), which follows hepatic hyperplasia and corresponds to the peak of hepatocyte apoptosis. In both phases, a decrease of the lipogenic enzyme activities has been detected. In treated animals, an alteration of mitochondrial lipid composition has also been found. The modified lipid microenvironment could be responsible for the decreased carrier activity which, in turn, may account for the reduced activities of the lipogenic enzymes.
Biochem Mol Biol Int 1999 Apr
PMID:Citrate carrier and lipogenic enzyme activities in lead nitrate-induced proliferative and apoptotic phase in rat liver. 1031 12

The yeast vacuole functions both as a degradative organelle and as a storage depot for small molecules and ions. Vacuoles are dynamic reticular structures that appear to alternately fuse and fragment as a function of growth stage and environment. Vac8p, an armadillo repeat-containing protein, has previously been shown to function both in vacuolar inheritance and in protein targeting from the cytoplasm to the vacuole. Both myristoylation and palmitoylation of Vac8p are required for its efficient localization to the vacuolar membrane (Y.-X. Wang, N. L. Catlett, and L. S. Weisman, J. Cell Biol. 140:1063-1074, 1998). We report that mutants with conditional defects in the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase (ACC1), display unusually multilobed vacuoles, similar to those observed in vac8 mutant cells. This vacuolar phenotype of acc1 mutant cells was shown biochemically to be accompanied by a reduced acylation of Vac8p which was alleviated by fatty acid supplementation. Consistent with the proposed defect of acc1 mutant cells in acylation of Vac8p, vacuolar membrane localization of Vac8p was impaired upon shifting acc1 mutant cells to nonpermissive condition. The function of Vac8p in protein targeting, on the other hand, was not affected under these conditions. These observations link fatty acid synthesis and availability to direct morphological alterations of an organellar membrane.
Mol Cell Biol 2000 May
PMID:A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p. 1075 83

Strain BR54 of Clostridium beijerinckii was derived from the wild type strain, NCIMB 8052, by mutagenesis with Tn1545 and selection for butanol tolerance. It harbours a single copy of Tn 1545 in a 435 bp intergenic region separating two convergently transcribed genes, accC and gldA. The former encodes biotin carboxylase (E.C.6.3.4.14), a subunit of acetyl-CoA carboxylase and the latter encodes glycerol dehydrogenase (E.C.1.1.1.6). Since Tn1545 generates outwardly directed transcripts from its right end, we considered the possibility that the transposon inserted in strain BR54 might affect the expression of the adjacent gldA gene. RT-PCR experiments revealed that the mutant, but not the wild type, contains antisense RNA corresponding to the gldA gene. Correlated with this, the level of glycerol dehydrogenase activity in the mutant was only 25% of that in the wild type when bacteria were grown with either glucose or glycerol as the fermentable substrate. We conclude that transcripts emerging from the right end of the conjugative transposon, Tn1545, can reduce the expression of the adjacent gldA gene by the generation of antisense RNA and that this is associated with a butanol-tolerant phenotype.
J Mol Microbiol Biotechnol 2000 Jan
PMID:Butanol tolerance of Clostridium beijerinckii NCIMB 8052 associated with down-regulation of gldA by antisense RNA. 1093 92

The TSC13/YDL015c gene was identified in a screen for suppressors of the calcium sensitivity of csg2Delta mutants that are defective in sphingolipid synthesis. The fatty acid moiety of sphingolipids in Saccharomyces cerevisiae is a very long chain fatty acid (VLCFA) that is synthesized by a microsomal enzyme system that lengthens the palmitate produced by cytosolic fatty acid synthase by two carbon units in each cycle of elongation. The TSC13 gene encodes a protein required for elongation, possibly the enoyl reductase that catalyzes the last step in each cycle of elongation. The tsc13 mutant accumulates high levels of long-chain bases as well as ceramides that harbor fatty acids with chain lengths shorter than 26 carbons. These phenotypes are exacerbated by the deletion of either the ELO2 or ELO3 gene, both of which have previously been shown to be required for VLCFA synthesis. Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in a tsc13 mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis. Tsc13p coimmunoprecipitates with Elo2p and Elo3p, suggesting that the elongating proteins are organized in a complex. Tsc13p localizes to the endoplasmic reticulum and is highly enriched in a novel structure marking nuclear-vacuolar junctions.
Mol Cell Biol 2001 Jan
PMID:Tsc13p is required for fatty acid elongation and localizes to a novel structure at the nuclear-vacuolar interface in Saccharomyces cerevisiae. 1111 86

A lipolytic domain (AOD9401) of human growth hormone (hGH) which resides in the carboxyl terminus of the molecule and contains the amino acid residues 177-191, has been synthesized using solid-phase peptide synthesis techniques. AOD9401 stimulated hormone-sensitive lipase and inhibited acetyl coenzyme A carboxylase (acetyl CoA carboxylase) in isolated rat adipose tissues, in a similar manner to the actions of the intact hGH molecule. The synthetic lipolytic domain mimicked the effect of the intact growth hormone on diacylglycerol release in adipocytes. Chronic treatment of obese Zucker rats with AOD9401 for 20 days reduced the body weight gain of the animals, and the average cell size of the adipocytes of the treated animals decreased from 110 to 80 microm in diameter. Unlike hGH, synthetic AOD9401 did not induce insulin resistance or glucose intolerance in the laboratory animals after chronic treatment. The results suggest that AOD9401 has the potential to be developed into a therapeutic agent for the control of obesity.
J Mol Endocrinol 2000 Dec
PMID:Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. 1111 8


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