Aberrant apolipoprotein C-III glycosylation in glycogen storage disease type III and IX

Ondruskova, Nina; Honzík, Tomáš; Kolářová, Hana; Pakanová, Zuzana; Mucha, Ján; Zeman, Jiří; Hansı́ková, Hana

doi:10.1016/j.metabol.2018.01.004

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…Loss-of-function mutations in GDE results in GSD type III (Figure 6A). Aberrant glycosylation in apolipoprotein C-III has been previously reported in this disease (Ondruskova et al, 2018). We hypothesize that Gde knockout mice would result in glycogen sequestration of glucosamine and altered Nlinked glycosylation.…”

Section: Protein Glycosylation Defects In Brain Regions With Pgbs In ...mentioning

confidence: 59%

“…Our data establish that dysregulated glycogen metabolism, resulting in PGBs, leads to defects in protein glycosylation. Abnormal glycosylation has been reported clinically in GSD type Ib, III, IV, and XIV (Den Hollander et al, 2007;Ondruskova et al, 2018). Additionally, profound protein hypoglycosylation was observed in patients with mutation in the ER-associated glucose-6-phosphate transporter that results in GSD Ib (Hayee et al, 2011).…”

Section: Discussionmentioning

confidence: 97%

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Brain glycogen serves as a critical glucosamine cache required for protein glycosylation

et al. 2021

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Section: Protein Glycosylation Defects In Brain Regions With Pgbs In ...mentioning

confidence: 59%

Section: Discussionmentioning

confidence: 97%

Brain glycogen serves as a critical glucosamine cache required for protein glycosylation

et al. 2021

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“…Analysis of apolipoprotein C-III, the marker of O-glycosylation defects, was performed as described previously [14]. Briefly, the apolipoprotein C-III-enriched fraction of serum proteins was obtained from whole serum using C8 SPE (Supelclean LC-8, 100 mg, SupelCo, Bellefonte, PA, USA).…”

Section: Analysis Of Apolipoprotein C-iiimentioning

confidence: 99%

N-Glycoprofiling of SLC35A2-CDG: Patient with a Novel Hemizygous Variant

et al. 2023

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Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by a defect in the process of protein glycosylation. In this work, we present a comprehensive glycoprofile analysis of a male patient with a novel missense variant in the SLC35A2 gene, coding a galactose transporter that translocates UDP-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi apparatus. Isoelectric focusing of serum transferrin, which resulted in a CDG type II pattern, was followed by structural analysis of transferrin and serum N-glycans, as well as the analysis of apolipoprotein CIII O-glycans by mass spectrometry. An abnormal serum N-glycoprofile with significantly increased levels of agalactosylated (Hex3HexNAc4-5 and Hex3HexNAc5Fuc1) and monogalactosylated (Hex4HexNAc4 ± NeuAc1) N-glycans was observed. Additionally, whole exome sequencing and Sanger sequencing revealed de novo hemizygous c.461T > C (p.Leu154Pro) mutation in the SLC35A2 gene. Based on the combination of biochemical, analytical, and genomic approaches, the set of distinctive N-glycan biomarkers was characterized. Potentially, the set of identified aberrant N-glycans can be specific for other variants causing SLC35A2-CDG and can distinguish this disorder from the other CDGs or other defects in the galactose metabolism.

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“…Genetic defects in O- glycosylation remarkably increase serum levels of ApoC-III 0a and decrease ApoC-III 1/2 glycoforms. High circulating levels of non-glycosylated ApoC-III 0 have been observed in GALNT2-CDG ( Zilmer et al., 2020 ), glycogen storage disease III and IX ( Ondruskova et al., 2018 ), and in the mutation of SLC35A1 (CMP-NeuAc transporter) ( Ng et al., 2017 ) and Golgi traffic/Golgi maintenance proteins (Conserved Oligomeric Golgi complex subunits (COG subunits) ( Foulquier et al., 2006 ), and vesicular H + -ATPase subunit ( Kornak et al., 2008 ). On the contrary, hypersialylation of ApoC-III has been observed due to overproduction of CMP-NeuAc caused by loss of feedback control in the activity of enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase, the main enzyme in CMP-NeuAc biosynthesis.…”

Section: Glycans On Apolipoproteins and Their Biological Rolementioning

confidence: 99%