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

---

Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The unresolved autotrophic CO2 fixation pathways in the sulfur-reducing Archaebacterium Thermoproteus neutrophilus and in the phototrophic Eubacterium Chloroflexus aurantiacus have been investigated. Autotrophically growing cultures were labelled with [1,4-13C1]succinate, and the 13C pattern in cell constituents was determined by 1H- and 13C-NMR spectroscopy of purified amino acids and other cell constituents. In both organisms succinate contributed to less than 10% of cell carbon, the major part of carbon originated from CO2. All cell constituents became 13C-labelled, but different patterns were observed in the two organisms. This proves that two different cyclic CO2 fixation pathways are operating in autotrophic carbon assimilation in both of which succinate is an intermediate. The 13C-labelling pattern in T. neutrophilus is consistent with the operation of a reductive citric acid cycle and rules out any other known autotrophic CO2 fixation pathway. Surprisingly, the proffered [1,4-13C1]succinate was partially converted to double-labelled [3,4-13C2]glutamate, but not to double-labelled aspartate. These findings suggest that the conversion of citrate to 2-oxoglutarate is readily reversible under the growth conditions used, and a reversible citrate cleavage reaction is proposed. The 13C-labelling pattern in C. aurantiacus disagrees with any of the established CO2 fixation pathways; it therefore demands a novel autotrophic CO2 fixation cycle in which 3-hydroxypropionate and succinate are likely intermediates. The bacterium excreted substantial amounts of 3-hydroxypropionate (5 mM) and succinate (0.5 mM) at the end of autotrophic growth. Autotrophically grown Chloroflexus cells contained acetyl-CoA carboxylase and propionyl-CoA carboxylase activity. These enzymes are proposed to be the main CO2-fixing enzymes resulting in malonyl-CoA and methylmalonyl-CoA formation; from these carboxylation products 3-hydroxypropionate and succinate, respectively, can be formed.
...
PMID:13C-NMR study of autotrophic CO2 fixation pathways in the sulfur-reducing Archaebacterium Thermoproteus neutrophilus and in the phototrophic Eubacterium Chloroflexus aurantiacus. 157 76

The activation of hepatic glycogen synthase by the amino-acid-induced cell swelling has been attributed to the stimulation of [glycogen-synthase]-phosphatase resulting from an increase in the intracellular content in glutamate and aspartate, and a decrease in intracellular Cl-, which is a compensatory response to cell swelling [Meijer, A. J., Baquet, A., Gustafson, L., van Woerkom, G. M. & Hue, L. (1992) J. Biol. Chem. 267, 5823-5828]. Here we studied whether the activation of acetyl-CoA carboxylase by cell swelling could be explained by the same mechanism. The activation of endogenous or purified acetyl-CoA carboxylase was measured in gel-filtered liver extracts or cytosols. No activation could be observed under basal conditions but a fivefold stimulation was obtained with concentrations of glutamate (20-25 mM) found in hepatocytes incubated with glutamine. A similar stimulation was also observed with other dicarboxylic acids such as malonate and succinate, or with metal ions like Mg2+, Ca2+ and Mn2+ (10 mM). The addition of 50-100 mM Cl- was found to inhibit the activation of acetyl-CoA carboxylase by some 20-30%. Mg2+ was also found to stimulate the activation of the endogenous glycogen synthase. The glutamate-stimulated and Mg(2+)-stimulated activation of glycogen synthase and acetyl-CoA carboxylase was unaffected by 10 microM inhibitor-2, a specific inhibitory protein of protein phosphatase-1, but could be nearly completely blocked by the phosphatase inhibitor microcystin-LR. Our data suggest that the amino-acid-induced activation of acetyl-CoA carboxylase and glycogen synthase in the liver occurs by a common ionic mechanism.
...
PMID:Mechanism of activation of liver acetyl-CoA carboxylase by cell swelling. 790 Oct 14

Incubation of hepatocytes under conditions known to increase their volume, i.e. with amino acids (glutamine, proline) or in hypo-osmotic medium, decreased carnitine palmitoyl-transferase I (CPT-I) activity. This effect of hepatocyte swelling was antagonized by okadaic acid and dibutyryl-cAMP. Physiological concentrations of glutamate inhibited CPT-I activity in digitonin-permeabilized hepatocytes but not in isolated mitochondria. Results suggest that the amino acid-induced inhibition of CPT-I shares a common mechanism with the amino acid-induced stimulation of acetyl-CoA carboxylase and glycogen synthase [(1993) Eur. J. Biochem. 217, 1083-1089].
...
PMID:Inhibition of carnitine palmitoyltransferase I by hepatocyte swelling. 791 May 67

The activation of hepatic acetyl-CoA carboxylase by Na(+)-cotransported amino acids such as glutamine has been attributed mainly to the stimulation of its dephosphorylation by accumulating dicarboxylic acids, e.g. glutamate. We report here on a hepatic species of protein phosphatase-2A that activates acetyl-CoA carboxylase in the presence of physiological concentrations of glutamate or Mg2+ and, under these conditions, accounts for virtually all the hepatic acetyl-CoA carboxylase phosphatase activity. Glutamate also stimulated the dephosphorylation of a synthetic pentadecapeptide encompassing the Ser-79 phosphorylation site of rat acetyl-CoA carboxylase, but did not affect the dephosphorylation of other substrates such as phosphorylase. Conversely, protamine, which stimulated the dephosphorylation of phosphorylase, inhibited the activation of acetyl-CoA carboxylase. A comparison with various species of muscle protein phosphatase-2A showed that the stimulatory effects of glutamate and Mg2+ on the acetyl-CoA carboxylase phosphatase activity are largely mediated by the regulatory A subunit. Glutamate and Mg2+ emerge from our study as novel regulators of protein phosphatase-2A when acting on acetyl-CoA carboxylase.
...
PMID:Activation of hepatic acetyl-CoA carboxylase by glutamate and Mg2+ is mediated by protein phosphatase-2A. 864 8

Certain amino acids such as glutamine and proline stimulate liver glycogen synthesis and lipogenesis. This implies cell swelling and leads to the activation of glycogen synthase and acetyl-CoA carboxylase by a common mechanism. This mechanism results from the cell response to swelling and involves a fall in intracellular concentration of chloride ions and an increase in intracellular concentration of glutamate and aspartate. These ions indeed regulate the protein phosphatases that activate glycogen synthase and acetyl-CoA carboxylase.
...
PMID:[Regulation of liver carbohydrate and lipid metabolism by cell volume]. 878 51

Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, an essential substrate for fatty acid biosynthesis and a potent inhibitor of fatty acid oxidation. Here, we provide evidence that glutamate may be a physiologically relevant activator of ACC. Glutamate induced the activation of both major isoforms of ACC, prepared from rat liver, heart, or white adipose tissue. In agreement with previous studies, a type 2A protein phosphatase contributed to the effects of glutamate on ACC. However, the protein phosphatase inhibitor microcystin LR did not abolish the effects of glutamate on ACC activity. Moreover, glutamate directly activated purified preparations of ACC when protein phosphatase activity was excluded. Phosphatase-independent ACC activation by glutamate was also reflected by polymerization of the enzyme as judged by size-exclusion chromatography. The sensitivity of ACC to direct activation by glutamate was diminished by treatment in vitro with AMP-activated protein kinase or cAMP-dependent protein kinase or by beta-adrenergic stimulation of intact adipose tissue. We conclude that glutamate, an abundant intracellular amino acid, induces ACC activation through complementary actions as a phosphatase activator and as a direct allosteric ligand for dephosphorylated ACC. This study supports the general hypothesis that amino acids fulfill important roles as signal molecules as well as intermediates in carbon and nitrogen metabolism.
...
PMID:Bimodal activation of acetyl-CoA carboxylase by glutamate. 1075 75

Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, a precursor in the biosynthesis of long-chain fatty acids, which have been implicated in physiological insulin secretion. The catalytic function of ACC is regulated by phosphorylation (inactive)-dephosphorylation (active). In this study we investigated whether similar regulatory mechanisms exist for ACC in the pancreatic islet beta-cell. ACC was quantitated in normal rat islets, human islets, and clonal beta-cells (HIT-15 or INS-1) using a [(14)C]bicarbonate fixation assay. In the beta-cell lysates, ACC was stimulated by magnesium in a concentration-dependent manner. Of all the dicarboxylic acids tested, only glutamate, albeit ineffective by itself, significantly potentiated magnesium-activated ACC in a concentration-dependent manner. ACC stimulation by glutamate and magnesium was maximally demonstrable in the cytosolic fraction; it was markedly reduced by okadaic acid (OKA) in concentrations (<50 nmol/l) that inhibited protein phosphatase 2A (PP2A). Furthermore, pretreatment of the cytosolic fraction with anti-PP2A serum attenuated the glutamate- and magnesium-mediated activation of ACC, thereby suggesting that ACC may be regulated by an OKA-sensitive PP2A-like enzyme. Streptavidin-agarose chromatography studies have indicated that glutamate- and magnesium-mediated effects on ACC are attributable to activation of ACC's dephosphorylation; this suggests that the stimulatory effects of glutamate and magnesium on ACC might involve activation of an OKA-sensitive PP2A-like enzyme that dephosphorylates and activates ACC. In our study, 5-amino-imidazolecarboxamide (AICA) riboside, a stimulator of AMP kinase, significantly inhibited glucose-mediated activation of ACC and insulin secretion from isolated beta-cells. Together, our data provide evidence for a unique regulatory mechanism for the activation of ACC in the pancreatic beta-cell, leading to the generation of physiological signals that may be relevant for physiological insulin secretion.
...
PMID:Activation of acetyl-CoA carboxylase by a glutamate- and magnesium-sensitive protein phosphatase in the islet beta-cell. 1142 79

We previously identified and characterized a glutamate- and magnesium-sensitive PP2A-like phosphatase (GAPP), which dephosphorylated and activated acetyl-CoA carboxylase (ACC) in the islet beta cell. Herein, we studied potential regulatory mechanisms by which GAPP is activated by glutamate and magnesium, and also quantitated the degree of activation, by glutamate- and magnesium, of ACC in normal rat islets and islets derived from the diabetic Goto-Kakizaki (GK) rat, a model for type 2 diabetes in humans. Our findings indicate that magnesium, but not glutamate, specifically activates the post-translational carboxylmethylation (CML) of the 36 kDa catalytic subunit of GAPP. Okadaic acid (OKA), which inhibits GAPP-mediated activation of ACC, also reduced the magnesium-stimulated CML of the catalytic subunit of GAPP in all the beta cell preparations studied. These data suggest that the CML step may be necessary for magnesium- and glutamate-mediated activation of ACC. We also observed a marked attenuation in magnesium- and glutamate-facilitated activation of ACC activity in islets derived from the GK rat. Together, our findings raise an interesting possibility that inhibition of GAPP-catalyzed inactivation of ACC (and subsequent reduction in the generation of long-chain fatty acids) could contribute toward the abnormalities in insulin secretion demonstrable in this animal model for type 2 diabetes.
...
PMID:Further evidence for the regulation of acetyl-CoA carboxylase activity by a glutamate- and magnesium-activated protein phosphatase in the pancreatic beta cell: defective regulation in the diabetic GK rat islet. 1580 88

Corynebacterium glutamicum strains are used for the fermentative production of L-glutamate. Five C. glutamicum deletion mutants were isolated by two rounds of selection for homologous recombination and identified by Southern blot analysis. The growth, glucose consumption and glutamate production of the mutants were analyzed and compared with the wild-type ATCC 13032 strain. Double disruption of dtsR1 (encoding a subunit of acetyl-CoA carboxylase complex) and pyc (encoding pyruvate carboxylase) caused efficient overproduction of L-glutamate in C. glutamicum; production was much higher than that of the wild-type strain and DeltadtsR1 strain under glutamate-inducing conditions. In the absence of any inducing conditions, the amount of glutamate produced by the double-deletion strain DeltadtsR1Deltapyc was more than that of the mutant DeltadtsR1. The activity of phosphoenolpyruvate carboxylase (PEPC) was found to be higher in the DeltadtsR1Deltapyc strain than in the DeltadtsR1 strain and the wild-type strain. Therefore, PEPC appears to be an important anaplerotic enzyme for glutamate synthesis in DeltadtsR1 derivatives. Moreover, this conclusion was confirmed by overexpression of ppc and pyc in the two double-deletion strains (DeltadtsR1Deltappc and DeltadtsR1Deltapyc), respectively. Based on the data generated in this investigation, we suggest a new method that will improve glutamate production strains and provide a better understanding of the interaction(s) between the anaplerotic pathway and fatty acid synthesis.
...
PMID:Double deletion of dtsR1 and pyc induce efficient L: -glutamate overproduction in Corynebacterium glutamicum. 1940 28

Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo(11)C-acetate and PET-CT scanning to show that colonic acetate crosses the blood-brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through (13)C high-resolution magic-angle-spinning that (13)C acetate from fermentation of (13)C-labelled carbohydrate in the colon increases hypothalamic (13)C acetate above baseline levels. Hypothalamic (13)C acetate regionally increases the (13)C labelling of the glutamate-glutamine and GABA neuroglial cycles, with hypothalamic (13)C lactate reaching higher levels than the 'remaining brain'. These observations suggest that acetate has a direct role in central appetite regulation.
...
PMID:The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. 2478 6


1 2 Next >>

---