RGD Reference Report - Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase. - Rat Genome Database

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Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase.

Authors: Konrad, RJ  Zhang, F  Hale, JE  Knierman, MD  Becker, GW  Kudlow, JE 
Citation: Konrad RJ, etal., Biochem Biophys Res Commun. 2002 Apr 26;293(1):207-12.
RGD ID: 9590171
Pubmed: (View Article at PubMed) PMID:12054585
DOI: Full-text: DOI:10.1016/S0006-291X(02)00200-0

We have previously shown that diabetogenic antibiotic streptozotocin (STZ), an analog of N-acetylglucosamine (GlcNAc), inhibits the enzyme O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase (O-GlcNAcase) which is responsible for the removal of O-GlcNAc from proteins. Alloxan, another beta-cell toxin is a uracil analog. Since the O-GlcNAc transferase (OGT) uses UDP-GlcNAc as a substrate, we investigated whether alloxan might interfere with the process of protein O-glycosylation by blocking OGT, a very abundant enzyme in beta-cells. In isolated pancreatic islets, alloxan almost completely blocked both glucosamine-induced and STZ-induced protein O-GlcNAcylation, suggesting that alloxan indeed was inhibiting (OGT). In order to show definitively that alloxan was inhibiting OGT activity, recombinant OGT was incubated with 0-10 mM alloxan, and OGT activity was measured directly by quantitating UDP-[(3)H]-GlcNAc incorporation into the recombinant protein substrate, nucleoporin p62. Under these conditions, OGT activity was completely inhibited by 1 mM alloxan with half-maximal inhibition achieved at a concentration of 0.1 mM alloxan. Together, these data demonstrate that alloxan is an inhibitor of OGT, and as such, is the first OGT inhibitor described.

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Ogt  (O-linked N-acetylglucosamine (GlcNAc) transferase)

Additional Information