Gas Chromatography-Mass Spectrometric Determinations of Iduronic and Glucuronic Acids in Glycosaminoglycans after Reduction of Carboxylic Group Using Sodium Borodeuteride

Toida, Toshihiko; Qiu, Guoning; Matsunaga, Takuya; Sagehashi, Yoshinori; Imanari, Toshio

doi:10.2116/analsci.8.799

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…The SMILEY solution for the blocked reaction IDOAASE4ly proposed transport of iduronic acid out of the cytosol in order to restore flux through the dermatan sulfate subsystem. These results suggest a transport function for iduronic acid out of the cytosol, which appears plausible as iduronic acid has been detected in urine (M. Fuller, personal communication; [ 43 , 47 ]. Iduronic acid was also identified as a root no-consumption metabolite in heparan sulfate degradation causing twelve blocked reactions.…”

Section: Resultsmentioning

confidence: 88%

The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions

2011

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BackgroundMetabolic network reconstructions formalize our knowledge of metabolism. Gaps in these networks pinpoint regions of metabolism where biological components and functions are "missing." At the same time, a major challenge in the post genomic era involves characterisation of missing biological components to complete genome annotation.ResultsWe used the human metabolic network reconstruction RECON 1 and established constraint-based modelling tools to uncover novel functions associated with human metabolism. Flux variability analysis identified 175 gaps in RECON 1 in the form of blocked reactions. These gaps were unevenly distributed within metabolic pathways but primarily found in the cytosol and often caused by compounds whose metabolic fate, rather than production, is unknown. Using a published algorithm, we computed gap-filling solutions comprised of non-organism specific metabolic reactions capable of bridging the identified gaps. These candidate solutions were found to be dependent upon the reaction environment of the blocked reaction. Importantly, we showed that automatically generated solutions could produce biologically realistic hypotheses of novel human metabolic reactions such as of the fate of iduronic acid following glycan degradation and of N-acetylglutamate in amino acid metabolism.ConclusionsThe results demonstrate how metabolic models can be utilised to direct hypotheses of novel metabolic functions in human metabolism; a process that we find is heavily reliant upon manual curation and biochemical insight. The effectiveness of a systems approach for novel biochemical pathway discovery in mammals is demonstrated and steps required to tailor future gap filling algorithms to mammalian metabolic networks are proposed.

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Section: Resultsmentioning

confidence: 88%

The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions

2011

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“…GlcUA Is Required for Inhibitory Activity-The oligosaccharide inhibitors were prepared from CSA polysaccharide that was shown to contain no IdoUA residues when analyzed by 1 H NMR (Ref. 23; data not shown). CSB, which contains IdoUA rather than GlcUA, did not substantially inhibit parasite adhesion to CSA (Fig.…”

Section: Dodecasaccharides With Four or Five 4-o-sulfatesmentioning

confidence: 99%

The Structural Motif in Chondroitin Sulfate for Adhesion ofPlasmodium falciparum-infected Erythrocytes Comprises Disaccharide Units of 4-O-Sulfated and Non-sulfated N-Acetylgalactosamine Linked to Glucuronic Acid

Chai¹,

Beeson²,

Lawson³

2002

Journal of Biological Chemistry

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An important characteristic of malaria parasite Plasmodium falciparum-infected red blood cells (IRBCs) is their ability to adhere to host endothelial cells and accumulate in various organs. Sequestration of IRBCs in the placenta, associated with excess perinatal and maternal mortality, is mediated in part by adhesion of parasites to the glycosaminoglycan chondroitin sulfate A (CSA) present on syncytiotrophoblasts lining the placental blood spaces. To define key structural features for parasite interactions, we isolated from CSA oligosaccharide fractions and established by electrospray mass spectrometry and high performance liquid chromatography disaccharide composition analysis their differing chain length, sulfate content, and sulfation pattern. Testing these defined oligosaccharide fragments for their ability to inhibit IRBC adhesion to immobilized CSA revealed the importance of non-sulfated disaccharide units in combination with 4-O-sulfated disaccharides for interaction with IRBCs. Selective removal of 6-O-sulfates from oligo-and polysaccharides to increase the proportion of non-sulfated disaccharides enhanced activity, indicating that 6-O-sulfation interferes with the interaction of CSA with IRBCs. Dodecasaccharides with four or five 4-O-sulfated and two or one non-sulfated disaccharide units, respectively, comprise the minimum chain length for effective interaction with IRBCs. Comparison of the activities of CSA and CSB oligoand polysaccharides with a similar sulfation pattern and content achieved from partial desulfation demonstrated that glucuronic acid rather than iduronic acid residues are important for IRBC binding.

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“…GAG samples were hydrolyzed by methanolysis, and the iduronic and glucuronic acids were derivatized to trimethylsilyl ethers prior to GC–MS [91]. The use of mass spectrometry (MS) coupled with GC allows separation and quantitation of sub-microgram quantities of the sugars.…”

Section: Gag Assay Methodsmentioning

confidence: 99%

Glycosaminoglycans detection methods: Applications of mass spectrometry

Kubaski

Osago

Mason

et al. 2017

Molecular Genetics and Metabolism

103

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Glycosaminoglycans (GAGs) are long blocks of negatively charged polysaccharides. They are one of the major components of the extracellular matrix and play multiple roles in different tissues and organs. The accumulation of undegraded GAGs causes mucopolysaccharidoses (MPS). GAGs are associated with other pathological conditions such as osteoarthritis, inflammation, diabetes mellitus, spinal cord injury, and cancer. The need for further understanding of GAG functions and mechanisms of action boosted the development of qualitative and quantitative (alcian blue, toluidine blue, paper and thin layer chromatography, gas chromatography, high pressure liquid chromatography, capillary electrophoresis, 1,9-dimethylmethylene blue, enzyme linked-immunosorbent assay, mass spectrometry) techniques. The availability of quantitative techniques has facilitated translational research on GAGs into the medical field for: 1) diagnosis, monitoring, and screening for MPS; 2) analysis of GAG synthetic and degradation pathways; and 3) determination of physiological and pathological roles of GAGs. This review provides a history of development of GAG assays and insights about the use of tandem mass spectrometry and its applications for GAG analysis.

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Gas Chromatography-Mass Spectrometric Determinations of Iduronic and Glucuronic Acids in Glycosaminoglycans after Reduction of Carboxylic Group Using Sodium Borodeuteride

Cited by 10 publications

References 24 publications

The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions

The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions

The Structural Motif in Chondroitin Sulfate for Adhesion ofPlasmodium falciparum-infected Erythrocytes Comprises Disaccharide Units of 4-O-Sulfated and Non-sulfated N-Acetylgalactosamine Linked to Glucuronic Acid

Glycosaminoglycans detection methods: Applications of mass spectrometry

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