ArticleThe Journal of biological chemistry2012
Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of α2-8-linked N-glycolylneuraminic acid to enzymatic cleavage.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Biosynthetic and genetic pathways related to sialic acid metabolism.The Journal of biological chemistry · 2026Review
- Cellular homeostasis of N-acetylneuraminic acid and non-canonical sialic acids is mediated by human N-acetylneuraminate lyase.Glycobiology · 2026Article
- Endothelial glycosylation and its emerging role in pulmonary vascular health and disease.Nature communications · 2025Review
- Combination of racotumomab immunotherapy with programmed death-1 blockade in a preclinical model of non-small cell lung cancer.Translational lung cancer research · 2025Article
- Inactivation of the CMAH gene and deficiency of Neu5Gc play a role in human brain evolution.Inflammation and regeneration · 2025Review
- Article
- Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases.Frontiers in neurology · 2024Review
- The vertebrate sialylation machinery: structure-function and molecular evolution of GT-29 sialyltransferases.Glycoconjugate journal · 2023Review
- Alteration of rhesus macaque serum N-glycome during infection with the human parasitic filarial nematode Brugia malayi.Scientific reports · 2022Article
- Comprehensive Analysis of Oligo/Polysialylglycoconjugates in Cancer Cell Lines.International journal of molecular sciences · 2022Article
- Dietary Neu5Ac Intervention Protects Against Atherosclerosis Associated With Human-Like Neu5Gc Loss-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Article
- Control of Innate Immunity by Sialic Acids in the Nervous Tissue.International journal of molecular sciences · 2020Review
- α2,3 linkage of sialic acid to a GPI anchor and an unpredicted GPI attachment site in human prion protein.The Journal of biological chemistry · 2020Article
- Determination of the Structural Integrity and Stability of Polysialic Acid during Alkaline and Thermal Treatment.Molecules (Basel, Switzerland) · 2019Article
- Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates.Nature microbiology · 2019Article
- Systems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns.Nature communications · 2018Article
- Keeping it trim: roles of neuraminidases in CNS function.Glycoconjugate journal · 2018Review
- Human evolutionary loss of epithelial Neu5Gc expression and species-specific susceptibility to cholera.PLoS pathogens · 2018Article
- Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc.Genome biology and evolution · 2018Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 5 countries.
Funding
Abstract
The sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative N-glycolylneuraminic acid (Neu5Gc) differ by one oxygen atom. CMP-Neu5Gc is synthesized from CMP-Neu5Ac, with Neu5Gc representing a highly variable fraction of total Sias in various tissues and among different species. The exception may be the brain, where Neu5Ac is abundant and Neu5Gc is reported to be rare. Here, we confirm this unusual pattern and its evolutionary conservation in additional samples from various species, concluding that brain Neu5Gc expression has been maintained at extremely low levels over hundreds of millions of years of vertebrate evolution. Most explanations for this pattern do not require maintaining neural Neu5Gc at such low levels. We hypothesized that resistance of α2-8-linked Neu5Gc to vertebrate sialidases is the detrimental effect requiring the relative absence of Neu5Gc from brain. This linkage is prominent in polysialic acid (polySia), a molecule with critical roles in vertebrate neural development. We show that Neu5Gc is incorporated into neural polySia and does not cause in vitro toxicity. Synthetic polymers of Neu5Ac and Neu5Gc showed that mammalian and bacterial sialidases are much less able to hydrolyze α2-8-linked Neu5Gc at the nonreducing terminus. Notably, this difference was not seen with acid-catalyzed hydrolysis of polySias. Molecular dynamics modeling indicates that differences in the three-dimensional conformation of terminal saccharides may partly explain reduced enzymatic activity. In keeping with this, polymers of N-propionylneuraminic acid are sensitive to sialidases. Resistance of Neu5Gc-containing polySia to sialidases provides a potential explanation for the rarity of Neu5Gc in the vertebrate brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.