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Changes in the properties of cytosolic acetyl-CoA carboxylase studied in cold-clamped liver samples from fed, starved and starved-refed rats.

ABSTRACT: We have used the cold-clamping technique to study the changes in acetyl-CoA carboxylase activity that occur in the cytosolic and mitochondrial fractions of the liver of fed, starved and starved-refed rats. No evidence was found for a role of the mitochondrial enzyme as a pool from which cytosolic carboxylase could be replenished upon refeeding of starved rats. Starvation for 24 h or 48 h induced changes in the expressed (assayed at 20 mM-citrate), total (citrate- and phosphatase-treated) and citrate-independent activities of cytosolic carboxylase, as well as in its Ka for citrate. The expressed/total activity ratio was low even in the fed state and was depressed further by starvation. The effects of refeeding occurred in two phases: an acute phase (approx. 1 h) in which the starvation-induced changes in Ka and expressed/total activity ratio were rapidly reversed, and a prolonged slow phase in which the two parameters attained values that were lower and higher, respectively, than those in the normal fed state. Refeeding also resulted in a gradual increase in citrate-independent activity of acetyl-CoA carboxylase. An additional marked increase in this activity occurred only in 48 h-starved-refed rats between 24 h and 48 h of refeeding. These findings are discussed in terms of the observed time courses of changes in lipogenic rates that occur in vivo in starved-refed rats and of the possible molecular mechanisms involved.

SUBMITTER: Moir AM

PROVIDER: S-EPMC1149730 | biostudies-other | 1990 Dec

REPOSITORIES: biostudies-other

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Mitochondrial acetyl-CoA carboxylase. Time course of mobilization/activation in liver of refed rats.

Project description:Fasted (48 h) rats were killed at 0, 2, 4, 6, 8, 12, 16, 20 and 24 h after they were refed on a high-carbohydrate diet. An increase in the maximal activity and quantity of cystolic acetyl-CoA carboxylase was found in liver of refed rats after a lag time of about 8 h. The increased quantity of cytosolic enzyme was attributable primarily to mobilization of mitochondrial storage forms and not to substantial increase in the rate of synthesis of acetyl-CoA carboxylase.

| S-EPMC1138765 | biostudies-other

Hepatic gene expression profiles during fed-fasted-refed state in mice.

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| S-EPMC10020372 | biostudies-literature

AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis.

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The hemolymph proteome of fed and starved Drosophila larvae.

Project description:The co-operation of specialized organ systems in complex multicellular organisms depends on effective chemical communication. Thus, body fluids (like blood, lymph or intraspinal fluid) contain myriads of signaling mediators apart from metabolites. Moreover, these fluids are also of crucial importance for immune and wound responses. Compositional analyses of human body fluids are therefore of paramount diagnostic importance. Further improving their comprehensiveness should increase our understanding of inter-organ communication. In arthropods, which have trachea for gas exchange and an open circulatory system, the single dominating interstitial fluid is the hemolymph. Accordingly, a detailed analysis of hemolymph composition should provide an especially comprehensive picture of chemical communication and defense in animals. Therefore we used an extensive protein fractionation workflow in combination with a discovery-driven proteomic approach to map out the detectable protein composition of hemolymph isolated from Drosophila larvae. Combined mass spectrometric analysis revealed more than 700 proteins extending far beyond the previously known Drosophila hemolymph proteome. Moreover, by comparing hemolymph isolated from either fed or starved larvae, we provide initial provisional insights concerning compositional changes in response to nutritional state. Storage proteins in particular were observed to be strongly reduced by starvation. Our hemolymph proteome catalog provides a rich basis for data mining, as exemplified by our identification of potential novel cytokines, as well as for future quantitative analyses by targeted proteomics.

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The sensitive to freezing3 mutation of Arabidopsis thaliana is a cold-sensitive allele of homomeric acetyl-CoA carboxylase that results in cold-induced cuticle deficiencies.

Project description:The sfr3 mutation causes freezing sensitivity in Arabidopsis thaliana. Mapping, sequencing, and transgenic complementation showed sfr3 to be a missense mutation in ACC1, an essential gene encoding homomeric (multifunctional) acetyl-CoA carboxylase. Cuticle permeability was compromised in the sfr3 mutant when plants were grown in the cold but not in the warm. Wax deposition on the inflorescence stem of cold-grown sfr3 plants was inhibited and the long-chain components of their leaf cuticular wax were reduced compared with wild-type plants. Thus, freezing sensitivity of sfr3 appears, from these results, to be due to cuticular deficiencies that develop during cold acclimation. These observations demonstrated the essential role of the cuticle in tolerance to freezing and drought.

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The dynamic organization of fungal acetyl-CoA carboxylase.

Project description:Acetyl-CoA carboxylases (ACCs) catalyse the committed step in fatty-acid biosynthesis: the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. They are important regulatory hubs for metabolic control and relevant drug targets for the treatment of the metabolic syndrome and cancer. Eukaryotic ACCs are single-chain multienzymes characterized by a large, non-catalytic central domain (CD), whose role in ACC regulation remains poorly characterized. Here we report the crystal structure of the yeast ACC CD, revealing a unique four-domain organization. A regulatory loop, which is phosphorylated at the key functional phosphorylation site of fungal ACC, wedges into a crevice between two domains of CD. Combining the yeast CD structure with intermediate and low-resolution data of larger fragments up to intact ACCs provides a comprehensive characterization of the dynamic fungal ACC architecture. In contrast to related carboxylases, large-scale conformational changes are required for substrate turnover, and are mediated by the CD under phosphorylation control.

| S-EPMC4833862 | biostudies-literature

Structure of a gene encoding a cytosolic acetyl-CoA carboxylase of hexaploid wheat.

Project description:An entire gene encoding wheat (var. Hard Red Winter Tam 107) acetyl-CoA carboxylase [ACCase; acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] has been cloned and sequenced. Comparison of the 12-kb genomic sequence with the 7.4-kb cDNA sequence reported previously revealed 29 introns. Within the coding region, the exon sequence is 98% identical to the known wheat cDNA sequence. A second ACCase gene was identified by sequencing fragments of genomic clones that include the first two exons and the first intron. Additional transcripts were detected by 5' and 3' RACE analysis (rapid amplification of cDNA ends). One set of transcripts had a 5' end sequence identical to the cDNA found previously and another set was identical to the gene reported here. The 3' RACE clones fall into four distinguishable sequence sets, bringing the number of ACCase sequences to six. None of these cDNA or genomic clones encodes a chloroplast targeting signal. Identification of six different sequences suggests that either the cytosolic ACCase genes are duplicated in the three chromosome sets in hexaploid wheat or that each of the six alleles of the cytosolic ACCase gene has a readily distinguishable DNA sequence.

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In vivo regulatory phosphorylation of the phosphoenolpyruvate carboxylase AtPPC1 in phosphate-starved Arabidopsis thaliana.

Project description:PEPC [PEP(phosphoenolpyruvate) carboxylase] is a tightly controlled cytosolic enzyme situated at a major branchpoint in plant metabolism. Accumulating evidence indicates important functions for PEPC and PPCK (PEPC kinase) in plant acclimation to nutritional P(i) deprivation. However, little is known about the genetic origin or phosphorylation status of native PEPCs from -P(i) (P(i)-deficient) plants. The transfer of Arabidopsis suspension cells or seedlings to -P(i) growth media resulted in: (i) the marked transcriptional upregulation of genes encoding the PEPC isoenzyme AtPPC1 (Arabidopsis thaliana PEPC1), and PPCK isoenzymes AtPPCK1 and AtPPCK2; (ii) >2-fold increases in PEPC specific activity and in the amount of an immunoreactive 107-kDa PEPC polypeptide (p107); and (iii) In vivo p107 phosphorylation as revealed by immunoblotting of clarified extracts with phosphosite-specific antibodies to Ser-11 (which could be reversed following P(i) resupply). Approx. 1.3 mg of PEPC was purified 660-fold from -P(i) suspension cells to apparent homogeneity with a specific activity of 22.3 units x mg(-1) of protein. Gel filtration, SDS/PAGE and immunoblotting demonstrated that purified PEPC exists as a 440-kDa homotetramer composed of identical p107 subunits. Sequencing of p107 tryptic and Asp-N peptides by tandem MS established that this PEPC is encoded by AtPPC1. P(i)-affinity PAGE coupled with immunoblotting indicated stoichiometric phosphorylation of the p107 subunits of AtPPC1 at its conserved Ser-11 phosphorylation site. Phosphorylation activated AtPPC1 at pH 7.3 by lowering its Km(PEP) and its sensitivity to inhibition by L-malate and L-aspartate, while enhancing activation by glucose 6-phosphate. Our results indicate that the simultaneous induction and In vivo phosphorylation activation of AtPPC1 contribute to the metabolic adaptations of -P(i) Arabidopsis.

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A capillary electrophoretic assay for acetyl coenzyme A carboxylase.

Project description:A simple off-column capillary electrophoretic (CE) assay for measuring acetyl coenzyme A carboxylase holoenzyme (holo-ACC) activity and inhibition was developed. The two reactions catalyzed by the holo-ACC components, biotin carboxylase (BC) and carboxyltransferase (CT), were simultaneously monitored in this assay. Acetyl coenzyme A (CoA), malonyl-CoA, adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were separated by capillary electrophoresis, and the depletion of ATP and acetyl-CoA as well as the production of ADP and malonyl-CoA were monitored. Inhibition of holo-ACC by the BC inhibitor, 2-amino-N,N-dibenzyloxazole-5-carboxamide, and the carboxyltransferase inhibitor, andrimid, was confirmed using this assay. A previously reported off-column CE assay for only the CT component of ACC was optimized, and an off-column CE assay for the BC component of ACC also was developed.

| S-EPMC3627828 | biostudies-literature

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