Carbohydrate-Processing Enzymes of the Lysosome

Stütz, Arnold; Wrodnigg, Tanja

doi:10.1016/bs.accb.2016.08.002

Cited by 18 publications

(5 citation statements)

References 389 publications

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“…The more potent inhibitory effect of SNAP compared to ONAP, could be due to the inherent intracellular stability of S-glycosides. In this regard, O-glycosides are commonly used to assay the activity of hexosaminidases, and it is known that mammalian cells have lysosomal, nuclear and cytoplasmic hexosaminidases that may cleave such substrates (Stutz and Wrodnigg, 2016). To determine if such hexosaminidase activity is prominent in HL-60 cells, we measured the HPLC elution profile of 2-napthelenemethanol (HONAP, hydrolyzed ONAP) and 2-naphthalenemethanethiol (HSNAP) standards spiked into the HL-60 cell culture supernatant (Fig.…”

Section: Resultsmentioning

confidence: 99%

Thioglycosides Are Efficient Metabolic Decoys of Glycosylation that Reduce Selectin Dependent Leukocyte Adhesion

Wang

Gao

Solar

et al. 2018

Cell Chemical Biology

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SUMMARY Metabolic decoys are synthetic analogs of naturally occurring biosynthetic acceptors. These compounds divert cellular biosynthetic pathways by acting as artificial substrates that usurp the activity of natural enzymes. While O-linked glycosides are common, they are only partially effective even at millimolar concentrations. In contrast, we report that N-acetylglucosamine (GlcNAc) incorporated into various thioglycosides robustly truncate cell-surface N- and O-linked glycan biosynthesis at 10–100μM concentrations. The >10 fold greater inhibition is in part due to the resistance of thioglycosides to hydrolysis by intracellular hexosaminidases. The thioglycosides reduce β-galactose incorporation into lactosamine chains, cell-surface sialyl Lewis-X expression, and leukocyte rolling on selectin-substrates including inflamed endothelial cells under fluid shear. Treatment of granulocytes with thioglycosides prior to murine infusion inhibited neutrophil homing to sites of acute inflammation and bone marrow by ~80–90%. Overall, thioglycosides represent an easy to synthesize class of efficient metabolic inhibitors/decoys. They reduce N-/O-linked glycan biosynthesis and inflammatory leukocyte accumulation.

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Section: Resultsmentioning

confidence: 99%

Thioglycosides Are Efficient Metabolic Decoys of Glycosylation that Reduce Selectin Dependent Leukocyte Adhesion

Wang

Gao

Solar

et al. 2018

Cell Chemical Biology

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“…146 Extensive research concerning the development of such stimuli-responsive polymersomes has been undertaken and previous reviews neatly summarise this vast field. 6,8,9,52,147,148 Considering that many diseases present distinct physiological fluctuations (often also localised in organs or tissues), polymersomes that are capable of responding to pH gradients, 149 enzyme overexpression, 150 changing redox potential, 151 and biochemical reactions 151,152 are of great interest in the context of drug delivery.…”

Section: Added Functionalities In Biodegradable Polymersomesmentioning

confidence: 99%

Polymersome-based protein drug delivery – quo vadis?

et al. 2023

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“…When this process is dysregulated, glycoproteins and other undegraded molecules accumulate in the lysosomes. Lysosomal storage diseases (LSDs) are inherited metabolic diseases which are caused by a deficiency of degradation enzymes, leading to abnormal build-up of a variety of toxic compounds [409]. Thus far, over 40 LSDs have been described and reported to mostly involve the skeleton, skin, brain and central nervous system [410].…”

Section: Disorders Of Lysosomal Carbohydrate-processingmentioning

confidence: 99%

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

Conte,

Sam,

Lefeber

et al. 2023

IJMS

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Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations. In this systematic review, we offer a comprehensive overview of IMDs linked to carbohydrate metabolism presenting that present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects. We identified 58 IMDs presenting with cardiac complications: 3 defects of sugar/sugar-linked transporters (GLUT3, GLUT10, THTR1); 2 disorders of the pentose phosphate pathway (G6PDH, TALDO); 9 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1); 29 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2); 15 carbohydrate-linked lysosomal storage diseases (CTSA, GBA1, GLA, GLB1, HEXB, IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, ARSB, GUSB, ARSK). With this systematic review we aim to raise awareness about the cardiac presentations in carbohydrate-linked IMDs and draw attention to carbohydrate-linked pathogenic mechanisms that may underlie cardiac complications.

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Carbohydrate-Processing Enzymes of the Lysosome

Cited by 18 publications

References 389 publications

Thioglycosides Are Efficient Metabolic Decoys of Glycosylation that Reduce Selectin Dependent Leukocyte Adhesion

Thioglycosides Are Efficient Metabolic Decoys of Glycosylation that Reduce Selectin Dependent Leukocyte Adhesion

Polymersome-based protein drug delivery – quo vadis?

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

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