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Animal Nutrition (Zhongguo Xu Mu Shou... Mar 2016Alpha-enolase (ENO1), also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic... (Review)
Review
Alpha-enolase (ENO1), also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. It is a multifunctional glycolytic enzyme involved in cellular stress, bacterial and fungal infections, autoantigen activities, the occurrence and metastasis of cancer, parasitic infections, and the growth, development and reproduction of organisms. This article mainly reviews the basic characteristics and biological functions of ENO1.
PubMed: 29767008
DOI: 10.1016/j.aninu.2016.02.005 -
Frontiers in Bioscience (Landmark... Mar 2017Transposon-mediated "directed" mutations occur at higher frequencies when beneficial than when detrimental and relieve the stress that causes them. The first and... (Review)
Review
Transposon-mediated "directed" mutations occur at higher frequencies when beneficial than when detrimental and relieve the stress that causes them. The first and best-studied example involves regulation of Insertion Sequence-5 (IS5) insertion into a specific activating site upstream of the glycerol utilization operon in , . This event promotes high level expression of the operon, allowing glycerol utilization in wild type cells under inhibitory conditions. The phosphoenolpyruvate-dependent, sugar transporting, phosphotransferase system (PTS) influences this process by regulating cytoplasmic glycerol-3-phosphate and cyclic AMP concentrations. Insertion frequencies are determined by IS5-specific tetranucleotide target sequences in stress-induced (DNA) duplex destabilization (SIDD) structures counteracted by two DNA binding proteins, GlpR and Crp which directly inhibit insertion, responding to cytoplasmic glycerol-3-phosphate and cyclic AMP, respectively. Expression of the master regulator of flagellar gene control, , is subject to activation by IS elements by a directed mechanism, and zinc-induced transposon-mediated zinc resistance has been demonstrated in . The use of DNA conformation and DNA binding proteins to control transposon hopping also occurs in eukaryotes.
Topics: Bacteria; Cupriavidus; DNA Transposable Elements; Escherichia coli; Eukaryota; Evolution, Molecular; Mutation; Operon; Phosphoenolpyruvate Sugar Phosphotransferase System; Zinc
PubMed: 28199212
DOI: 10.2741/4553 -
Frontiers in Cell and Developmental... 2023Metabolic reprogramming is commonly accompanied by alterations in the expression of metabolic enzymes. These metabolic enzymes not only catalyze the intracellular... (Review)
Review
Metabolic reprogramming is commonly accompanied by alterations in the expression of metabolic enzymes. These metabolic enzymes not only catalyze the intracellular metabolic reaction, but also participate in a series of molecular events to regulate tumor initiation and development. Thus, these enzymes may act as promising therapeutic targets for tumor management. Phosphoenolpyruvate carboxykinases (PCKs) are the key enzymes involved in gluconeogenesis, which mediates the conversion of oxaloacetate into phosphoenolpyruvate. Two isoforms of PCK, namely cytosolic PCK1 and mitochondrial PCK2, has been found. PCK not only participates in the metabolic adaptation, but also regulates immune response and signaling pathways for tumor progression. In this review, we discussed the regulatory mechanisms of PCKs expression including transcription and post-translational modification. We also summarized the function of PCKs in tumor progression in different cellular contexts and explores its role in developing promising therapeutic opportunities.
PubMed: 37250903
DOI: 10.3389/fcell.2023.1196226 -
Annals of Botany Nov 2023This review summarizes recent advances in our understanding of Crassulacean Acid Metabolism (CAM) by integrating evolutionary, ecological, physiological, metabolic and... (Review)
Review
BACKGROUND AND SCOPE
This review summarizes recent advances in our understanding of Crassulacean Acid Metabolism (CAM) by integrating evolutionary, ecological, physiological, metabolic and molecular perspectives. A number of key control loops which moderate the expression of CAM phases, and their metabolic and molecular control, are explored. These include nocturnal stomatal opening, activation of phosphoenolpyruvate carboxylase by a specific protein kinase, interactions with circadian clock control, as well as daytime decarboxylation and activation of Rubisco. The vacuolar storage and release of malic acid and the interplay between the supply and demand for carbohydrate reserves are also key metabolic control points.
FUTURE OPPORTUNITIES
We identify open questions and opportunities, with experimentation informed by top-down molecular modelling approaches allied with bottom-up mechanistic modelling systems. For example, mining transcriptomic datasets using high-speed systems approaches will help to identify targets for future genetic manipulation experiments to define the regulation of CAM (whether circadian or metabolic control). We emphasize that inferences arising from computational approaches or advanced nuclear sequencing techniques can identify potential genes and transcription factors as regulatory targets. However, these outputs then require systematic evaluation, using genetic manipulation in key model organisms over a developmental progression, combining gene silencing and metabolic flux analysis and modelling to define functionality across the CAM day-night cycle. From an evolutionary perspective, the origins and function of CAM succulents and responses to water deficits are set against the mesophyll and hydraulic limitations imposed by cell and tissue succulence in contrasting morphological lineages. We highlight the interplay between traits across shoots (3D vein density, mesophyll conductance and cell shrinkage) and roots (xylem embolism and segmentation). Thus, molecular, biophysical and biochemical processes help to curtail water losses and exploit rapid rehydration during restorative rain events. In the face of a changing climate, we hope such approaches will stimulate opportunities for future research.
Topics: Crassulacean Acid Metabolism; Photosynthesis; Phosphoenolpyruvate Carboxylase; Biological Evolution; Water
PubMed: 37742290
DOI: 10.1093/aob/mcad142 -
International Journal of Molecular... Nov 2021Some metabolic pathways involve two different cell components, for instance, cytosol and mitochondria, with metabolites traffic occurring from cytosol to mitochondria... (Review)
Review
Some metabolic pathways involve two different cell components, for instance, cytosol and mitochondria, with metabolites traffic occurring from cytosol to mitochondria and vice versa, as seen in both glycolysis and gluconeogenesis. However, the knowledge on the role of mitochondrial transport within these two glucose metabolic pathways remains poorly understood, due to controversial information available in published literature. In what follows, we discuss achievements, knowledge gaps, and perspectives on the role of mitochondrial transport in glycolysis and gluconeogenesis. We firstly describe the experimental approaches for quick and easy investigation of mitochondrial transport, with respect to cell metabolic diversity. In addition, we depict the mitochondrial shuttles by which NADH formed in glycolysis is oxidized, the mitochondrial transport of phosphoenolpyruvate in the light of the occurrence of the mitochondrial pyruvate kinase, and the mitochondrial transport and metabolism of L-lactate due to the L-lactate translocators and to the mitochondrial L-lactate dehydrogenase located in the inner mitochondrial compartment.
Topics: Animals; Biological Transport; Gluconeogenesis; Glycolysis; Humans; Mitochondria; NAD; Phosphoenolpyruvate; Pyruvate Kinase
PubMed: 34884425
DOI: 10.3390/ijms222312620 -
American Journal of Physiology.... Jan 2023Acute exercise increases liver gluconeogenesis to supply glucose to working muscles. Concurrently, elevated liver lipid breakdown fuels the high energetic cost of...
Acute exercise increases liver gluconeogenesis to supply glucose to working muscles. Concurrently, elevated liver lipid breakdown fuels the high energetic cost of gluconeogenesis. This functional coupling between liver gluconeogenesis and lipid oxidation has been proposed to underlie the ability of regular exercise to enhance liver mitochondrial oxidative metabolism and decrease liver steatosis in individuals with nonalcoholic fatty liver disease. Herein we tested whether repeated bouts of increased hepatic gluconeogenesis are necessary for exercise training to lower liver lipids. Experiments used diet-induced obese mice lacking hepatic phosphoenolpyruvate carboxykinase 1 (KO) to inhibit gluconeogenesis and wild-type (WT) littermates. H/C metabolic flux analysis quantified glucose and mitochondrial oxidative fluxes in untrained mice at rest and during acute exercise. Circulating and tissue metabolite levels were determined during sedentary conditions, acute exercise, and refeeding postexercise. Mice also underwent 6 wk of treadmill running protocols to define hepatic and extrahepatic adaptations to exercise training. Untrained KO mice were unable to maintain euglycemia during acute exercise resulting from an inability to increase gluconeogenesis. Liver triacylglycerides were elevated after acute exercise and circulating β-hydroxybutyrate was higher during postexercise refeeding in untrained KO mice. In contrast, exercise training prevented liver triacylglyceride accumulation in KO mice. This was accompanied by pronounced increases in indices of skeletal muscle mitochondrial oxidative metabolism in KO mice. Together, these results show that hepatic gluconeogenesis is dispensable for exercise training to reduce liver lipids. This may be due to responses in ketone body metabolism and/or metabolic adaptations in skeletal muscle to exercise. Exercise training reduces hepatic steatosis partly through enhanced hepatic terminal oxidation. During acute exercise, hepatic gluconeogenesis is elevated to match the heightened rate of muscle glucose uptake and maintain glucose homeostasis. It has been postulated that the hepatic energetic stress induced by elevating gluconeogenesis during acute exercise is a key stimulus underlying the beneficial metabolic responses to exercise training. This study shows that hepatic gluconeogenesis is not necessary for exercise training to lower liver lipids.
Topics: Mice; Animals; Phosphoenolpyruvate; Glucose; Liver; Gluconeogenesis; 3-Hydroxybutyric Acid
PubMed: 36351254
DOI: 10.1152/ajpendo.00222.2022 -
American Journal of Physiology. Renal... Apr 2020There are substantial sex differences in renal structure and ammonia metabolism that correlate with differences in expression of proteins involved in ammonia generation...
There are substantial sex differences in renal structure and ammonia metabolism that correlate with differences in expression of proteins involved in ammonia generation and transport. This study determined the role of testis-derived testosterone in these differences. We studied 4-mo-old male C57BL/6 mice 4 and 8 wk after either bilateral orchiectomy (ORCH) or sham-operated control surgery and determined the effect of testosterone replacement to reverse the effects of ORCH. Finally, we determined the cellular expression of androgen receptor (AR), testosterone's canonical target receptor. ORCH decreased kidney and proximal tubule size, and testosterone replacement reversed this effect. ORCH increased ammonia excretion in a testosterone-dependent fashion; this occurred despite similar food intake, which is the primary component of endogenous acid production. ORCH increased expression of both phosphopyruvate, a major ammonia-generating protein, and Na-K-2Cl cotransporter, which mediates thick ascending limb ammonia reabsorption; these changes were reversed with testosterone replacement. Orchiectomy also decreased expression of Na/H exchanger isoform 3, which mediates proximal tubule ammonia secretion, in a testosterone-dependent pattern. Finally, ARs are expressed throughout the proximal tubule in both the male and female kidney. Testosterone, possibly acting through ARs, has dramatic effects on kidney and proximal tubule size and decreases ammonia excretion through its effects on several key proteins involved in ammonia metabolism.
Topics: Ammonia; Animals; Female; Hormone Replacement Therapy; Kidney; Male; Mice, Inbred C57BL; Orchiectomy; Phosphoenolpyruvate Carboxykinase (ATP); Receptors, Androgen; Renal Elimination; Sex Factors; Sodium-Bicarbonate Symporters; Sodium-Hydrogen Exchanger 3; Solute Carrier Family 12, Member 1; Testosterone
PubMed: 32116019
DOI: 10.1152/ajprenal.00560.2019 -
Cell Death & Disease Aug 2022On glucose restriction, epithelial cells can undergo entosis, a cell-in-cell cannibalistic process, to allow considerable withstanding to this metabolic stress. Thus, we...
On glucose restriction, epithelial cells can undergo entosis, a cell-in-cell cannibalistic process, to allow considerable withstanding to this metabolic stress. Thus, we hypothesized that reduced protein glycosylation might participate in the activation of this cell survival pathway. Glucose deprivation promoted entosis in an MCF7 breast carcinoma model, as evaluated by direct inspection under the microscope, or revealed by a shift to apoptosis + necrosis in cells undergoing entosis treated with a Rho-GTPase kinase inhibitor (ROCKi). In this context, curbing protein glycosylation defects with N-acetyl-glucosamine partially rescued entosis, whereas limiting glycosylation in the presence of glucose with tunicamycin or NGI-1, but not with other unrelated ER-stress inducers such as thapsigargin or amino-acid limitation, stimulated entosis. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M; PCK2) is upregulated by glucose deprivation, thereby enhancing cell survival. Therefore, we presumed that PEPCK-M could play a role in this process by offsetting key metabolites into glycosyl moieties using alternative substrates. PEPCK-M inhibition using iPEPCK-2 promoted entosis in the absence of glucose, whereas its overexpression inhibited entosis. PEPCK-M inhibition had a direct role on total protein glycosylation as determined by Concanavalin A binding, and the specific ratio of fully glycosylated LAMP1 or E-cadherin. The content of metabolites, and the fluxes from C-glutamine label into glycolytic intermediates up to glucose-6-phosphate, and ribose- and ribulose-5-phosphate, was dependent on PEPCK-M content as measured by GC/MS. All in all, we demonstrate for the first time that protein glycosylation defects precede and initiate the entosis process and implicates PEPCK-M in this survival program to dampen the consequences of glucose deprivation. These results have broad implications to our understanding of tumor metabolism and treatment strategies.
Topics: Breast Neoplasms; Entosis; Female; Glucose; Glycosylation; Humans; Phosphoenolpyruvate Carboxykinase (ATP)
PubMed: 36002449
DOI: 10.1038/s41419-022-05177-x -
ACS Central Science Feb 2020Phosphorylation of alcohols is a fundamentally important reaction in both life science and physical science. Product phosphate monoesters play key roles in living...
Phosphorylation of alcohols is a fundamentally important reaction in both life science and physical science. Product phosphate monoesters play key roles in living organisms, natural products, pharmaceuticals, and organic materials. Most of the chemical methods to date for synthesizing phosphate monoesters, however, require multistep sequences or are limited to specific types of substrates possibly due to harsh conditions. An alternative way to enable the simple production of phosphate monoesters from highly functionalized precursor alcohols is, thus, highly desired. We report herein a catalytic phosphorylation of alcohols with high functional group tolerance using tetrabutylammonium hydrogen sulfate (TBAHS) and phosphoenolpyruvic acid monopotassium salt (PEP-K) as the catalyst and phosphoryl donor, respectively. This method enables the direct introduction of a nonprotected phosphate group to the hydroxy group of a diverse menu of alcohol substrates, including functionalized small molecules, carbohydrates, and unprotected peptides. Nuclear magnetic resonance, mass spectrometric, and density functional theory analyses suggest that an unprecedented mixed anhydride species, generated from PEP-K and TBAHS, acts as an active phosphoryl donor in this reaction. This operationally simple and chemoselective catalytic phosphorylation allows for the efficient production of densely functionalized -phosphorylated compounds, which are useful in diverse fields including biology and medicine.
PubMed: 32123747
DOI: 10.1021/acscentsci.9b01272 -
Plant Physiology and Biochemistry : PPB Nov 2022Three plant-type phosphoenolpyruvate carboxylase (PPC1 to PPC3) and two phosphoenolpyruvate carboxylase kinase (PPCKs: PPCK1 and 2) genes are present in the Arabidopsis...
Three plant-type phosphoenolpyruvate carboxylase (PPC1 to PPC3) and two phosphoenolpyruvate carboxylase kinase (PPCKs: PPCK1 and 2) genes are present in the Arabidopsis thaliana genome. In seeds, all PPC genes were found to be expressed. Examination of individual ppc mutants showed little reduction of PEPC protein and global activity, with the notable exception of PPC2 which represent the most abundant PEPC in dry seeds. Ppc mutants exhibited moderately lower seed parameters (weight, area, yield, germination kinetics) than wild type. In contrast, ppck1-had much altered (decreased) yield. At the molecular level, ppc3-was found to be significantly deficient in global seed nitrogen (nitrate, amino-acids, and soluble protein pools). Also, N-deficiency was much more marked in ppck1-, which exhibited a tremendous loss of 95% and 90% in nitrate and proteins, respectively. The line ppck2-had accumulated amino-acids but lower levels of soluble proteins. Regarding carboxylic acid pools, Krebs cycle intermediates were found to be diminished in all mutants; this was accompanied by a consistent decrease in ATP. Lipids were stable in ppc mutants, however ppck1-seeds accumulated more lipids while ppck2-seeds showed high level of polyunsaturated fatty acid oleic and linolenic (omega 3). Altogether, the results indicate that the complete PEPC and PPCK family are needed for normal C/N metabolism ratio, growth, development, yield and quality of the seed.
Topics: Adenosine Triphosphate; Arabidopsis; Carboxylic Acids; Isoenzymes; Lipids; Nitrates; Nitrogen; Phosphoenolpyruvate Carboxylase; Protein Serine-Threonine Kinases; Seeds
PubMed: 36099810
DOI: 10.1016/j.plaphy.2022.08.012