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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of phosphoenolpyruvate carboxylase (PEPC, EC4.1.1.31) for the C4 photosynthesis is known to be regulated mainly in response to light/dark transitions through reversible phosphorylation by a specific protein kinase (PK). PEPC-PK with an M(r) of 30 kDa was purified about 1.4 million-fold to homogeneity from maize leaves and characterized. The purified PEPC-PK was readily inactivated under mild oxidative conditions, but the activity could be recovered by dithiothreitol (DTT). The recovery by DTT was strongly accelerated by thioredoxin (Trx) from E. coli. Trxs of plant origin such as Trx-m from spinach chloroplast and Trx-h from rice cytoplasm were also effective. These results suggest the possibility of PEPC-PK being redox-regulated via Trx in vivo.
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PMID:Thioredoxin-mediated reductive activation of a protein kinase for the regulatory phosphorylation of C4-form phosphoenolpyruvate carboxylase from maize. 1177 21

Thioredoxin-interacting protein (Txnip) is a ubiquitous protein that binds with high affinity to thioredoxin and inhibits its ability to reduce sulfhydryl groups via NADPH oxidation. HcB-19 mice contain a nonsense mutation in Txnip that eliminates its expression. Unlike normal animals, HcB-19 mice have approximately 3-fold increase in insulin levels when fasted. The C-peptide/insulin ratio is normal, suggesting that the hyperinsulinemia is due to increased insulin secretion. Fasted HcB-19 mice are hypoglycemic, hypertriglyceridemic, and have higher than normal levels of ketone bodies. Ablation of pancreatic beta-cells with streptozotocin completely blocks the fasting-induced hypoglycemia/hypertriglyceridemia, suggesting that these abnormalities are due to excess insulin secretion. This is supported by increased hepatic mRNA levels of the insulin-inducible, lipogenic transcription factor sterol-responsive element-binding protein-1c and two of its targets, acetyl-CoA carboxylase and fatty acid synthase. During a prolonged fast, the hyperinsulinemia up-regulates lipogenesis but fails to down-regulate hepatic phosphoenolpyruvate carboxykinase mRNA expression. Hepatic ratios of reduced:oxidized glutathione, established regulators of gluconeogenic/glycolytic/lipogenic enzymes, were elevated 30% in HcB-19 mice, suggesting a loss of Txnip-enhanced sulfhydryl reduction. The altered hepatic enzymatic profiles of HcB-19 mice divert phosphoenolpyruvate to glyceroneogenesis and lipogenesis rather than gluconeogenesis. Our findings implicate Txnip-modulated sulfhydryl redox as a central regulator of insulin secretion in beta-cells and regulation of many of the branch-points of gluconeogenesis/glycolysis/lipogenesis.
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PMID:Mice lacking thioredoxin-interacting protein provide evidence linking cellular redox state to appropriate response to nutritional signals. 1504 87

Through a positional cloning approach, the thioredoxin-interacting protein gene (Txnip) was recently identified as causal for a form of combined hyperlipidemia in mice (Bodnar, J. S., A. Chatterjee, L. W. Castellani, D. A. Ross, J. Ohmen, J. Cavalcoli, C. Wu, K. M. Dains, J. Catanese, M. Chu, S. S. Sheth, K. Charugundla, P. Demant, D. B. West, P. de Jong, and A. J. Lusis. 2002. Positional cloning of the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30: 110-116). We now show that Txnip-deficient mice in the fed state exhibit a metabolic profile similar to fasted mice, including increased levels of plasma ketone bodies and free fatty acids, decreased glucose, and increased hepatic expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and acyl-CoA oxidase. Dramatic differences in the expression of key metabolic enzymes were also observed in other tissues, and the fat-to-muscle ratio of Txnip-deficient mice was increased by approximately 40%. We demonstrate an effect of Txnip on the redox status, as the Txnip-deficient mice in the fed state had a significant increase in the ratio of NADH to NAD(+). Surprisingly, we observed that Txnip-deficient mice and wild-type mice had similar levels of thioredoxin activity, suggesting that the effects of Txnip deficiency may be mediated in part by other interactions. These results indicate a role for Txnip in the metabolic response to feeding and the maintenance of the redox status.
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PMID:Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition. 1552 Apr 47

The death effector domain (DED) of the mammalian apoptosis mediator, Fas-associated death domain protein (FADD), induces Escherichia coli cell death under aerobic culture conditions, yet the mechanisms by which FADD-DED induces cell death are not fully understood. Oxidative stress has been implicated as one of the mechanisms. Using a proteomic approach and validation by coexpression analysis, we illustrate that overexpression of FADD-DED in E. coli invokes protein expression changes that facilitate conversion of pro-oxidant NADH into antioxidant NADPH. Typically, isocitrate dehydrogenase, phosphoenolpyruvate carboxykinase, and pyruvate kinase are downregulated and malate dehydrogenase is upregulated. We reasoned that such a change in E. coli cells is an active response to reduce the size of the NADH pool, thereby decreasing the level of ROS generation. From the coexpression studies, we observed that DNA binding protein Hns, which induces growth arrest when overexpressed heterologously, alleviated the cell killing effect of FADD-DED. FADD-DED was expressed as a noncovalently linked multimeric protein in the membrane of E. coli. Exogenous treatment of E. coli cells with FADD-DED in the presence of a membrane component induced cell death, which was accompanied by a shift of the redox balance and a decrease in the cellular ATP level. Cell death was blocked by prior expression of thioredoxin. Localization of FADD-DED to the membrane may shift the cells into a state that stimulates and fuels ROS generation. The cell death mechanism mediated by ROS may mimic antibiotic-mediated bacterial cell death or Bax-mediated apoptosis in mammalian cells. Our results provide a common mechanistic feature of ROS-involved cell death throughout prokaryotes and eukaryotes.
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PMID:Localization of the death effector domain of Fas-associated death domain protein into the membrane of Escherichia coli induces reactive oxygen species-involved cell death. 2007 Jan 22

Tuberculosis remains a major health concern worldwide. Eradication of its causative agent, the bacterial pathogen Mycobacterium tuberculosis, is particularly challenging due to a vast reservoir of latent carriers of the disease. Despite the misleading terminology of a so-called dormant state associated with latent infections, the bacteria have to maintain basic metabolic activities. Hypoxic conditions have been widely used as an in vitro system to study this dormancy. Such studies identified a rearrangement of central carbon metabolism to exploit fermentative processes caused by the lack of oxygen. Phosphoenolpyruvate carboxykinase (Pck; EC 4.1.1.32) is the enzyme at the center of these metabolic rearrangements. Although Pck is associated with gluconeogenesis under standard growth conditions, the enzyme can catalyze the reverse reaction, supporting anaplerosis of the tricarboxylic acid cycle, under conditions leading to slowed or stopped bacterial replication. To study the mechanisms that regulate the switch between two Pck functions, we systematically investigated factors influencing the gluconeogenic and anaplerotic reaction kinetics. We demonstrate that a reducing environment, as found under hypoxia-triggered non-replicating conditions, accelerates the reaction in the anaplerotic direction. Furthermore, we identified proteins that interact with Pck. The interaction between Pck and the reduced form of mycobacterial thioredoxin, gene expression of which is increased under hypoxic conditions, also increased the Pck anaplerotic activity. We thus propose that a reducing environment and the protein-protein interaction with thioredoxin in particular enable the Pck anaplerotic function under fermentative growth conditions.
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PMID:Mycobacterium tuberculosis phosphoenolpyruvate carboxykinase is regulated by redox mechanisms and interaction with thioredoxin. 2465 83