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 regulation of acetyl-CoA carboxylase (ACC) by glucose and other fuel molecules has been examined in Fao Reuber hepatoma cells and Syrian hamster insulin tumor (HIT) cells in order to determine whether lipogenic substrates acutely alter ACC activity and to examine the mechanism of such regulation. In Fao cells, preincubated in simple medium without substrates, glucose addition results in a rapid activation of ACC. This effect, mimicked by other fuels such as lactate, is characterized by an increase in enzyme Vmax and a decrease in the activation constant for citrate. Several lines of evidence indicate that this activation of ACC is due to enzyme dephosphorylation, including the kinetic changes observed, the persistence of enzyme activation through ACC isolation, the necessity of inclusion of sodium fluoride/EDTA in the cell lysis buffer for preservation of the glucose-induced change, and the direct demonstration of diminished 32P-labeling of ACC after glucose exposure. Identical effects of glucose are also observed in HIT cells, although the ACC activation is smaller in magnitude and less sensitive than that observed in Fao cells. Other insulin secretagogues such as glutamine, lactate, and isobutylmethylxanthine are also found to activate HIT ACC. Others have suggested that glucose-induced changes in malonyl-CoA in beta-cells may be linked to glucose-induced insulin secretion. However, studies conducted in late passage HIT cells, which fail to secrete insulin in response to glucose stimulation, reveal the same glucose-induced activation seen in early passages, secretion-competent HIT cells, suggesting that glucose-induced ACC activation is not by itself sufficient to provoke insulin secretion. Taken together, these findings indicate that glucose and other fuel molecules can play a major role in the rapid regulation of the fatty acid synthesis pathway. The activation of fatty acid synthesis by substrate-induced ACC dephosphorylation insures ultimate fuel storage of glucose-derived carbon as fatty acid, while substrate-induced increases in the ACC product, malonyl CoA, would serve to simultaneously limit the rate of fatty acid oxidation through its allosteric regulation of carnitine palmitoyltransferase I.
...
PMID:Glucose regulation of acetyl-CoA carboxylase in hepatoma and islet cells. 134 95

Incubation of hepatocytes in conditions known to increase their volume, i.e. with amino acids or in hypo-osmotic media, resulted in the parallel activation of glycogen synthase and acetyl-CoA carboxylase. The activation of both enzymes by glutamine was antagonized by the addition of raffinose to prevent cell swelling, or by glucagon and microcystin. The findings are consistent with the involvement of a common mechanism for the activation of the two enzymes.
...
PMID:Swelling of rat hepatocytes activates acetyl-CoA carboxylase in parallel to glycogen synthase. 168 Mar 22

Biotin carboxylase [biotin-carboxyl-carrier-protein:carbon-dioxide ligase (ADP-forming), EC 6.3.4.14] is the enzyme mediating the first step of the acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] reaction. We screened an Escherichia coli DNA library and a DNA fragment carrying the biotin carboxylase gene fabG, and its flanking regions were cloned. The gene for biotin carboxyl carrier protein was found 13 base pairs upstream of the fabG gene. Nucleotide sequencing of the recombinant plasmids revealed that the fabG codes for a 449-amino acid residue protein with a calculated molecular weight of 49,320, a value in good agreement with that of 51,000 determined by SDS/polyacrylamide gel electrophoresis of the purified enzyme. The deduced amino acid sequence of biotin carboxylase is also consistent with the partial amino acid sequence determined by Edman degradation. The primary structure of this enzyme exhibits a high homology with those of other biotin-dependent enzymes and carbamoyl-phosphate synthetase [carbon-dioxide:L-glutamine amino-ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.5.5]; therefore, all these enzymes probably function through the same mechanism of reaction.
...
PMID:Acetyl-CoA carboxylase from Escherichia coli: gene organization and nucleotide sequence of the biotin carboxylase subunit. 168 20

Double immunofluorescence staining showed carbonic anhydrase and glutamine synthetase in the same astrocytes. Carbamoylphosphate synthase II, which catalyzes the first committed step in pyrimidine biosynthesis, was also immunostained in astrocytes. The results suggested that in the astrocytes carbonic anhydrase and glutamine synthetase could provide the substrates, bicarbonate and glutamine, for pyrimidine biosynthesis. In the oligodendrocytes acetyl-CoA carboxylase was colocalized with carbonic anhydrase, and fatty acid synthase was immunostained in the same cell-type. As well as providing bicarbonate to initiate fatty acid synthesis in oligodendrocytes, the carbonic anhydrase in oligodendrocytes could recycle the carbon dioxide generated during this process.
...
PMID:Immunostaining of carbamoylphosphate synthase II and fatty acid synthase in glial cells in rat, mouse, and hamster brains suggests roles for carbonic anhydrase in biosynthetic processes. 168 28

The utilization of lactate, glucose, 3-hydroxybutyrate, and glutamine has been studied in isolated brain cells from early newborn rats. Isolated brain cells actively utilized these substrates, showing saturation at concentrations near physiological levels during the perinatal period. The rate of lactate utilization was 2.5-fold greater than that observed for glucose, 3-hydroxybutyrate, or glutamine, suggesting that lactate is the main metabolic substrate for the brain immediately after birth. The apparent Km for glucose utilization suggested that this process is limited by the activity of hexokinase. However, lactate, 3-hydroxybutyrate, and glutamine utilization seems to be limited by their transport through the plasma membrane. The presence of fatty acid-free bovine serum albumin (BSA) in the incubation medium significantly increased the rate of lipogenesis from lactate or 3-hydroxybutyrate, although this was balanced by the decrease in their rates of oxidation in the same circumstances. BSA did not affect the rate of glucose utilization. The effect of BSA was due not to the removal of free fatty acid, but possibly to the binding of long-chain acyl-CoA, resulting in the disinhibition of acetyl-CoA carboxylase and citrate carrier.
...
PMID:Lactate utilization by isolated cells from early neonatal rat brain. 191 82

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 possible role played by albumin in regulating brain metabolism during development has been studied. The effects of fatty acid-free BSA on lactate, glucose, 3-hydroxybutyrate, and glutamine oxidation and lipogenesis by rat neurons and astrocytes from primary culture were studied. The rate of lactate oxidation and lipogenesis by neurons and astrocytes in the presence of BSA greatly exceeded that observed for glucose, 3-hydroxybutyrate, or glutamine, suggesting that lactate may be a key substrate for brain development. BSA strongly stimulated the rate of lactate, 3-hydroxybutyrate, and glutamine incorporation into lipids in both neurons (677%, 726%, and 250%, respectively) and astrocytes (415%, 393%, and 215%, respectively), possibly by binding long-chain acyl-CoA excesses, potent inhibitors of acetyl-CoA carboxylase. However, BSA decreased the rate of lipogenesis from glucose in both neurons (34%) and astrocytes (55%), probably by inhibiting glycerol-borne phospholipid synthesis. BSA significantly increased the rates of lactate (61%) and glucose (32%) oxidation by astrocytes but not those of 3-hydroxybutyrate and glutamine, suggesting that BSA may stimulate pyruvate oxidation. However, in neurons BSA did not affect the rate of oxidation of any of the substrates tested, which suggests that pyruvate oxidation is regulated differently in neurons and astrocytes. The results suggest that lactate is the most important substrate for both neurons and astrocytes, stressing the role played by lactate in brain development. Our results also suggest that serum albumin may control brain development by fostering metabolism for growth and differentiation purposes.
...
PMID:Regulation of lactate metabolism by albumin in rat neurons and astrocytes from primary culture. 810 80

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

Incubation of isolated hepatocytes with glutamine or proline or in hypotonic media is known to activate glycogen synthase and acetyl-CoA carboxylase as a result of cell swelling. We report here that the same experimental conditions caused an activation of phosphatidylinositol 3-kinase and p70 ribosomal protein S6 kinase (p70 S6 kinase) but did not modify the activity of p42 mitogen-activated protein kinase. In addition, rapamycin, an inhibitor of p70 S6 kinase activation, prevented the amino acid- and hypotonicity-induced activation of p70 S6 kinase but did not block the activation of glycogen synthase and acetyl-CoA carboxylase, thus ruling out p70 S6 kinase as a necessary component in the activation pathway. By contrast, wortmannin or LY294002, inhibitors of phosphatidylinositol 3-kinase, completely blocked the activation of phosphatidylinositol 3-kinase and p70 S6 kinase and partly blocked the activation of glycogen synthase and acetyl-CoA carboxylase. Therefore, phosphatidylinositol 3-kinase might be a component of the signaling pathway that is triggered by cell swelling and is responsible, at least in part, for the activation of glycogen synthase and acetyl-CoA carboxylase. Incubation of hepatocytes with 0.1 microM epidermal growth factor doubled the activity of p42 mitogen-activated protein kinase without activating glycogen synthase.
...
PMID:Protein kinase signaling pathway triggered by cell swelling and involved in the activation of glycogen synthase and acetyl-CoA carboxylase in isolated rat hepatocytes. 866 1


1 2 3 Next >>

---