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International Journal of Molecular... May 2023Phosphoglucomutase 1 (PGM1) is a key enzyme for the regulation of energy metabolism from glycogen and glycolysis, as it catalyzes the interconversion of glucose...
Phosphoglucomutase 1 (PGM1) is a key enzyme for the regulation of energy metabolism from glycogen and glycolysis, as it catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate. PGM1 deficiency is an autosomal recessive disorder characterized by a highly heterogenous clinical spectrum, including hypoglycemia, cleft palate, liver dysfunction, growth delay, exercise intolerance, and dilated cardiomyopathy. Abnormal protein glycosylation has been observed in this disease. Oral supplementation with D-galactose efficiently restores protein glycosylation by replenishing the lacking pool of UDP-galactose, and rescues some symptoms, such as hypoglycemia, hepatopathy, and growth delay. However, D-galactose effects on skeletal muscle and heart symptoms remain unclear. In this study, we established an in vitro muscle model for PGM1 deficiency to investigate the role of PGM1 and the effect of D-galactose on nucleotide sugars and energy metabolism. Genome-editing of C2C12 myoblasts via CRISPR/Cas9 resulted in (mouse homologue of human , according to updated nomenclature) knockout clones, which showed impaired maturation to myotubes. No difference was found for steady-state levels of nucleotide sugars, while dynamic flux analysis based on C6-galactose suggested a block in the use of galactose for energy production in knockout myoblasts. Subsequent analyses revealed a lower basal respiration and mitochondrial ATP production capacity in the knockout myoblasts and myotubes, which were not restored by D-galactose. In conclusion, an in vitro mouse muscle cell model has been established to study the muscle-specific metabolic mechanisms in PGM1 deficiency, which suggested that galactose was unable to restore the reduced energy production capacity.
Topics: Animals; Mice; Galactose; Glucose; Homeostasis; Hypoglycemia; Muscle Fibers, Skeletal; Muscle, Skeletal; Nucleotides; Phosphates; Phosphoglucomutase
PubMed: 37175952
DOI: 10.3390/ijms24098247 -
Journal of Experimental Botany Mar 2023This article comments on: . 2023. Stress response requires an efficient glycogen and central carbon metabolism connection by phosphoglucomutases in cyanobacteria....
This article comments on: . 2023. Stress response requires an efficient glycogen and central carbon metabolism connection by phosphoglucomutases in cyanobacteria. Journal of Experimental Botany , 1532–1550
Topics: Phosphoglucomutase; Synechocystis; Bacterial Proteins
PubMed: 36913621
DOI: 10.1093/jxb/erac513 -
JIMD Reports Mar 2023We report successful heart transplantation in a phosphoglucomutase 1 deficient (PGM1-CDG) patient. She presented with facial dysmorphism, bifid uvula and structural...
We report successful heart transplantation in a phosphoglucomutase 1 deficient (PGM1-CDG) patient. She presented with facial dysmorphism, bifid uvula and structural heart defects. Newborn screening was positive for classic galactosemia. The patient was on a galactose-free diet for 8 months. Eventually, whole exome sequencing excluded the galactosemia and revealed PGM1-CDG. Oral D-galactose therapy was started. Rapid deterioration of the progressive dilated cardiomyopathy prompted heart transplantation at the age of 12 months. Cardiac function was stable in the first 18 months of follow-up, and hematologic, hepatic, and endocrine laboratory findings improved during D-galactose therapy. The latter therapy improves several systemic symptoms and biochemical abnormalities in PGM1-CDG but does not correct the heart failure related to cardiomyopathy. Heart transplantation has so far only been described in DOLK-CDG.
PubMed: 36873091
DOI: 10.1002/jmd2.12350 -
International Journal of Molecular... Jan 2023Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung...
Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung infections. HIES that is autosomally dominant in the signal transducer and activator of transcription 3 (STAT3), and autosomal recessive mutations in phosphoglucomutase 3 (PGM3) have been reported in humans. An early diagnosis, based on clinical suspicion and immunological assessments, is challenging. Patients' metabolomics, proteomics, and cytokine profiles were compared to DOCK 8-deficient and atopic dermatitis patients. The PGM3 metabolomics profile identified significant dysregulation in hypotaurine, hypoxanthine, uridine, and ribothymidine. The eight proteins involved include bifunctional arginine demethylase and lysyl hydroxylase (JMJD1B), type 1 protein phosphatase inhibitor 4 (PPI 4), and platelet factor 4 which aligned with an increased level of the cytokine GCSF. Patients with STAT3 deficiency, on the other hand, showed significant dysregulation in eight metabolites, including an increase in protocatechuic acid, seven proteins including ceruloplasmin, and a plasma protease C1 inhibitor, in addition to cytokine VEGF being dysregulated. Using multi-omics profiling, we identified the dysregulation of endothelial growth factor (EGFR) and tumor necrosis factor (TNF) signaling pathways in PGM3 and STAT3 patients, respectively. Our findings may serve as a stepping stone for larger prospective HIES clinical cohorts to validate their future use as biomarkers.
Topics: Humans; Immunoglobulin E; Phosphoglucomutase; STAT3 Transcription Factor; Multiomics; Prospective Studies; Job Syndrome; Mutation; Cytokines
PubMed: 36768728
DOI: 10.3390/ijms24032406 -
Journal of Lasers in Medical Sciences 2022There are documents about the biological effects of blue light radiation on different organisms. An understanding of the molecular mechanism of radiation effects on...
There are documents about the biological effects of blue light radiation on different organisms. An understanding of the molecular mechanism of radiation effects on biological samples is an important event which has attracted researchers' attention. Determining the critical dysregulated proteins of following blue light radiation is the aim of this study. 22 differentially expressed proteins of in response to 300 lux of blue light were extracted from the related literature. Experimental, text mining and co-expression connections between the queried proteins were assessed via the STRING database. The maps were compared and the critical proteins were identified. Among the 21 queried proteins, six individuals including heat shock HSP70 protein, 20S proteasome subunit, 26S proteasome subunit P45, Aspartate aminotransferase, phosphopyruvate hydratase, and phosphoglucomutase were highlighted as the critical proteins in response to blue light radiation. The finding indicates that protein homeostasis and glycogen synthesis are affected by blue light radiation. Due to the critical roles of proteins as enzymes and structural elements in life maintenance and involvement of glycogen synthesis in energy consumption, blue light radiation can be considered as a life promotional agent in future investigations.
PubMed: 36743131
DOI: 10.34172/jlms.2022.47 -
International Journal of Molecular... Jan 2023Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal...
Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal transduction pathways in mammalian cells, are shown to be regulated by LiCl. LiCl can negatively control the expression and activity of , a phosphoglucomutase that influences sugar metabolism in yeast. In the presence of galactose, when yeast cells are challenged by LiCl, the phosphoglucomutase activity of PGM2p is decreased, causing an increase in the concentration of toxic galactose metabolism intermediates that result in cell sensitivity. Here, we report that the null yeast mutant strains ∆ and ∆ exhibit increased LiCl sensitivity on galactose-containing media. Additionally, we demonstrate that and modulate the translational level of mRNA, and the observed alteration in translation seems to be associated with the 5'-untranslated region (UTR) of mRNA. Furthermore, we observe that and influence, to varying degrees, the translation of other mRNAs that carry different 5'-UTR secondary structures.
Topics: Lithium Chloride; Saccharomyces cerevisiae; RNA, Messenger; Phosphoglucomutase; Galactose; Saccharomyces cerevisiae Proteins; DEAD-box RNA Helicases
PubMed: 36675300
DOI: 10.3390/ijms24021785 -
Annals of Botany Nov 2023Crassulacean acid metabolism (CAM) is a specialized type of photosynthesis characterized by a diel pattern of stomatal opening at night and closure during the day, which...
The starch-deficient plastidic PHOSPHOGLUCOMUTASE mutant of the constitutive crassulacean acid metabolism (CAM) species Kalanchoë fedtschenkoi impacts diel regulation and timing of stomatal CO2 responsiveness.
BACKGROUND AND AIMS
Crassulacean acid metabolism (CAM) is a specialized type of photosynthesis characterized by a diel pattern of stomatal opening at night and closure during the day, which increases water-use efficiency. Starch degradation is a key regulator of CAM, providing phosphoenolpyruvate as a substrate in the mesophyll for nocturnal assimilation of CO2. Growing recognition of a key role for starch degradation in C3 photosynthesis guard cells for mediating daytime stomatal opening presents the possibility that starch degradation might also impact CAM by regulating the provision of energy and osmolytes to increase guard cell turgor and drive stomatal opening at night. In this study, we tested the hypothesis that the timing of diel starch turnover in CAM guard cells has been reprogrammed during evolution to enable nocturnal stomatal opening and daytime closure.
METHODS
Biochemical and genetic characterization of wild-type and starch-deficient RNAi lines of Kalanchoë fedtschenkoi with reduced activity of plastidic phosphoglucomutase (PGM) constituted a preliminary approach for the understanding of starch metabolism and its implications for stomatal regulation in CAM plants.
KEY RESULTS
Starch deficiency reduced nocturnal net CO2 uptake but had negligible impact on nocturnal stomatal opening. In contrast, daytime stomatal closure was reduced in magnitude and duration in the starch-deficient rPGM RNAi lines, and their stomata were unable to remain closed in response to elevated concentrations of atmospheric CO2 administered during the day. Curtailed daytime stomatal closure was linked to higher soluble sugar contents in the epidermis and mesophyll.
CONCLUSIONS
Nocturnal stomatal opening is not reliant upon starch degradation, but starch biosynthesis is an important sink for carbohydrates, ensuring daytime stomatal closure in this CAM species.
Topics: Crassulacean Acid Metabolism; Kalanchoe; Phosphoglucomutase; Carbon Dioxide; Starch; Photosynthesis
PubMed: 36661206
DOI: 10.1093/aob/mcad017 -
Glycobiology Mar 2023During our biochemical characterization of select bacterial phosphatases belonging to the haloacid dehalogenase superfamily of hydrolases, we discovered a strong bias of...
During our biochemical characterization of select bacterial phosphatases belonging to the haloacid dehalogenase superfamily of hydrolases, we discovered a strong bias of Salmonella YidA for glucose-1-phosphate (Glc-1-P) over galactose-1-phosphate (Gal-1-P). We sought to exploit this ability of YidA to discriminate these two sugar-phosphate epimers in a simple coupled assay that could be a substitute for current cumbersome alternatives. To this end, we focused on Gal-1-P uridylyltransferase (GalT) that is defective in individuals with classical galactosemia, an inborn disorder. GalT catalyzes the conversion of Gal-1-P and UDP-glucose to Glc-1-P and UDP-galactose. When recombinant YidA was coupled to GalT, the final orthophosphate product (generated from selective hydrolysis of Glc-1-P by YidA) could be easily measured using the inexpensive malachite green reagent. When this new YidA-based colorimetric assay was benchmarked using a recombinant Duarte GalT variant, it yielded kcat/Km values that are ~2.5-fold higher than the standard coupled assay that employs phosphoglucomutase and glucose-6-phosphate dehydrogenase. Although the simpler design of our new GalT coupled assay might find appeal in diagnostics, a testable expectation, we spotlight the GalT example to showcase the untapped potential of sugar-phosphate phosphatases with distinctive substrate-recognition properties for measuring the activity of various metabolic enzymes (e.g. trehalose-6-phosphate synthase, N-acetyl-glucosamine-6-phosphate deacetylase, phosphofructokinase).
Topics: Humans; Enzyme Assays; Phosphoric Monoester Hydrolases; Sugars; Uridine Diphosphate Glucose; UTP-Hexose-1-Phosphate Uridylyltransferase
PubMed: 36585843
DOI: 10.1093/glycob/cwac085 -
Molecules (Basel, Switzerland) Dec 2022An anti-biofilm that can inhibit the matrix of biofilm formation is necessary to prevent recurrent and chronic infection. This study aimed to design compounds with a...
An anti-biofilm that can inhibit the matrix of biofilm formation is necessary to prevent recurrent and chronic infection. This study aimed to design compounds with a new mechanism through competitive inhibitory activity against phosphomannomutase/phosphoglucomutase (PMM/PGM), using in vitro assessment and a computational (in silico) approach. The active site of PMM/PGM was assessed through molecular redocking using L-tartaric acid as the native ligand and other small molecules, such as glucaric acid, D-sorbitol, and ascorbic acid. The docking program set the small molecules to the active site, showing a stable complex formation. Analysis of structural similarity, bioavailability, absorption, distribution, metabolism, excretion, and toxicity properties proved the potential application of ligands as an anti-biofilm. In vitro assessment with crystal violet showed that the ligands could reach up to 95.87% inhibition at different concentrations. The nitrocellulose membrane and scanning electron microscopic visualization showed that the untreated biofilm was denser than the ligand-treated biofilm.
Topics: Pseudomonas aeruginosa; Ligands; Phosphoglucomutase; Catalytic Domain; Biofilms; Anti-Bacterial Agents
PubMed: 36558064
DOI: 10.3390/molecules27248935 -
Genes Nov 2022Sweet potato (Ipomoea batatas), an important root crop, has storage roots rich in starch that are edible and serve as a raw material in bioenergy production. Increasing...
Sweet potato (Ipomoea batatas), an important root crop, has storage roots rich in starch that are edible and serve as a raw material in bioenergy production. Increasing the storage-root starch contents is a key sweet potato breeding goal. Phosphoglucomutase (PGM) is the catalytic enzyme for the interconversion of glucose-6-phosphate and glucose-1-phosphate, precursors in the plant starch synthetic pathway. Plant PGMs have plastidial and cytosolic isoforms, based on their subcellular localization. Here, , containing 22 exons and 21 introns, was cloned from the sweet potato line Xu 781. This gene was highly expressed in the storage roots and leaves, and its expression was induced by exogenous sucrose treatments. The mature IbpPGM protein was successfully expressed in when a 73-aa chloroplastic transit peptide detected in the N-terminus was excised. The subcellular localization confirmed that IbpPGM was localized to the chloroplasts. The low-starch sweet potato cultivar Lizixiang -overexpression lines showed significantly increased starch, glucose, and fructose levels but a decreased sucrose level. Additionally, the expression levels of the starch synthetic pathway genes in the storage roots were up-regulated to different extents. Thus, significantly increased the starch content of the sweet potato storage roots, which makes it a candidate gene for the genetic engineering of the sweet potato.
Topics: Starch; Ipomoea batatas; Phosphoglucomutase; Plant Roots; Plant Breeding; Sucrose
PubMed: 36553501
DOI: 10.3390/genes13122234