Glucuronyl C5-epimerase: an enzyme converting glucuronic acid to iduronic acid in heparan sulfate/heparin biosynthesis
2010 (English)In: Progress in molecular biology and translational science, ISSN 1877-1173, Vol. 93, 59-78 p.Article, review/survey (Refereed) Published
The glucuronyl C5 epimerase (HSepi) is one of the modification enzymes involved in biosynthesis of heparan sulfate (HS) and heparin, catalyzing the epimerization of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) at polymer level. IdoA is critical for HS and heparin to interact with protein ligands, because of its flexible conformation. Although the enzyme recognizes both GlcA and IdoA as substrates catalyzing a reversible reaction of the hexuronic acids in vitro, the reaction appears irreversible in vivo. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality accompanied with kidney agenesis, premature lung, and skeletal malformations, demonstrating that the single gene coded enzyme is essential for animal development. Elimination of the enzyme resulted in abnormal HS and heparin structure that completely lacks IdoA residues. Loss of 2-O-sulfation due to lacking IdoA in HS chains appears compensated by increased N- and O-sulfation of the glucosamine residues. Recombinant HSepi is used to generate HS/heparin related compounds having potential to be used for therapeutic purposes.
Place, publisher, year, edition, pages
2010. Vol. 93, 59-78 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-135468DOI: 10.1016/S1877-1173(10)93004-4ISI: 000282063400004PubMedID: 20807641OAI: oai:DiVA.org:uu-135468DiVA: diva2:375085