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Metabolic Regulator (metabolic + regulator)
Selected AbstractsAMP-activated protein kinase and cancerACTA PHYSIOLOGICA, Issue 1 2009W. Wang Abstract AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Elevated AMP/ATP ratio activates AMPK, which inhibits energy-consuming processes and activates energy-producing processes to restore the energy homeostasis inside the cell. AMPK activators, metformin and thiazolidinediones, are used for the treatment of type II diabetes. Recently, reports have indicated that AMPK may also be a beneficial target for cancer treatment. Cancer cells have characteristic metabolic changes different from normal cells and, being a key metabolic regulator, AMPK may regulate the switch. AMPK may act to inhibit tumorigenesis through regulation of cell growth, cell proliferation, autophagy, stress responses and cell polarity. [source] The importance of a functional trehalose biosynthetic pathway for the life of yeasts and fungiFEMS YEAST RESEARCH, Issue 4-5 2004Carlos Gancedo Abstract The view of the role of trehalose in yeast has changed in the last few years. For a long time considered a reserve carbohydrate, it gained new importance when its function in the acquisition of thermotolerance was demonstrated. More recently the cellular processes in which the trehalose biosynthetic pathway has been implicated range from the control of glycolysis to sporulation and infectivity by certain fungal pathogens. There is now enough experimental evidence to conclude that trehalose 6-phosphate, an intermediate of trehalose biosynthesis, is an important metabolic regulator in such different organisms as yeasts or plants. Its inhibition of hexokinase plays a key role in the control of the glycolytic flux in Saccharomyces cerevisiae but other, likely important, sites of action are still unknown. We present examples of the phenotypes produced by mutations in the two steps of the trehalose biosynthetic pathway in different yeasts and fungi, and whenever possible examine the molecular explanations advanced to interpret them. [source] Evolutionary analysis of fructose 2,6-bisphosphate metabolismIUBMB LIFE, Issue 3 2006Paul A. M. Michels Abstract Fructose 2,6-bisphosphate is a potent metabolic regulator in eukaryotic organisms; it affects the activity of key enzymes of the glycolytic and gluconeogenic pathways. The enzymes responsible for its synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2) are present in representatives of all major eukaryotic taxa. Results from a bioinformatics analysis of genome databases suggest that very early in evolution, in a common ancestor of all extant eukaryotes, distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate. Subsequently, in different phylogenetic lineages duplications of the gene of the bifunctional enzyme occurred, allowing the development of distinct isoenzymes for expression in different tissues, at specific developmental stages or under different nutritional conditions. Independently in different lineages of many unicellular eukaryotes one of the domains of the different PFK-2/FBPase-2 isoforms has undergone substitutions of critical catalytic residues, or deletions rendering some enzymes monofunctional. In a considerable number of other unicellular eukaryotes, mainly parasitic organisms, the enzyme seems to have been lost altogether. Besides the catalytic core, the PFK-2/FBPase-2 has often N- and C-terminal extensions which show little sequence conservation. The N-terminal extension in particular can vary considerably in length, and seems to have acquired motifs which, in a lineage-specific manner, may be responsible for regulation of catalytic activities, by phosphorylation or ligand binding, or for mediating protein-protein interactions. IUBMB Life, 58: 133 - 141, 2006 [source] An inhibited conformation for the protein kinase domain of the Saccharomyces cerevisiae AMPK homolog Snf1ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010Michael J. Rudolph AMP-activated protein kinase (AMPK) is a master metabolic regulator for controlling cellular energy homeostasis. Its homolog in yeast, SNF1, is activated in response to glucose depletion and other stresses. The catalytic (,) subunit of AMPK/SNF1 in yeast (Snf1) contains a protein Ser/Thr kinase domain (KD), an auto-inhibitory domain (AID) and a region that mediates interactions with the two regulatory (, and ,) subunits. Here, the crystal structure of residues 41,440 of Snf1, which include the KD and AID, is reported at 2.4,Å resolution. The AID is completely disordered in the crystal. A new inhibited conformation of the KD is observed in a DFG-out conformation and with the glycine-rich loop adopting a structure that blocks ATP binding to the active site. [source] Expanding roles for AMP-activated protein kinase in neuronal survival and autophagyBIOESSAYS, Issue 9 2009Jeroen Poels Abstract AMP-activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti-diabetic drugs, exerts its actions by AMPK activation. However, while the functions of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted. [source] Hypoxia and low-nutrition double stress induces aggressiveness in a murine model of melanomaCANCER SCIENCE, Issue 5 2009Tsuyoshi Osawa Antiangiogenic therapy is a potent cancer treatment, however, the possibility of recurrence and resistance to this approach remains. Here we show that hypoxia and low-nutrition double-deprivation stress induces reversible tumor aggressiveness. In a stress-cycle-dependent manner, murine melanoma cells showed morphological changes, up-regulated phospho-Akt, and abnormal regulation of multiple genes including fibroblast growth factor-21, a metabolic regulator, resulting in increased cell proliferation in vitro, and increased tumorigenesis and invasive potential in vivo. In this system, altered cellular metabolism participates in the adaptation of tumor to the double-deprivation stress. Our results suggest the targeting of a minor population of cancer cells resistant to both hypoxia and low nutrition to be an effective new antitumor strategy in combination with antiangiogenic therapy. (Cancer Sci 2009; 100: 844,851) [source] | ||||||||||