Biosynthesis of dermatan sulfate. I. Formation of L iduronic acid residues

A. Malmstrom, L. A. Fransson, M. Hook, U. Lindahl

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Abstract

L [14C]Iduronic acid containing sulfated galactosaminoglycans were formed by incubation of a fibroblast particulate fraction with UDP D [14]glucuronic acid, UDP N acetylgalactosamine, and sulfate donor (3 phosphoadenylylsulfate). The formation of L iduronic acid was strongly promoted by concomitant sulfation of the polymer. In the absence of sulfate donor 5 to 10% of the [14C]uronic acid residues were L iduronic acid. However, when 3 phosphoadenylylsulfate was included in the incubation mixture the amount of L iduronic acid in the product increased 3 to 5 fold. Furthermore, approximately the same quantity of L [14C]iduronic acid was recovered from the product formed in a pulse chase experiment where incorporation of 14C isotope preceded sulfation. It was therefore concluded that C 5 inversion of D glucuronic acid to L iduronic acid occurred on the polymer level as shown previously for the biosynthesis of heparin. This conclusion was supported by the finding that no L [14C]iduronic acid could be detected in the UDP hexuronic acid pool during this experiment. Nonsulfated and sulfated [14C]galactosaminoglycan products were degraded separately with chondroitinase AC. The nonsulfated products afforded primarily disaccharide and a small amount of tetrasaccharide, while the sulfated products yielded, in addition, a considerable amount of larger oligosaccharides. Tetrasaccharides from nonsulfated products contained L iduronic acid indicating that C 5 inversion at solitary sites can occur in the absence of sulfation of adjacent hexosamine moieties. The larger oligosaccharides obtained after chondroitinase AC digestion of sulfated products yielded L iduronic acid upon acid hydrolysis and were susceptible to chondroitinase ABC digestion. The split products were almost exclusively 4 sulfated disaccharides. These results demonstrate that formation of blocks of L iduronic acid containing repeat periods is associated with 4 sulfation of adjacent hexosamine moieties.

Original languageEnglish (US)
Pages (from-to)3419-3425
Number of pages7
JournalJournal of Biological Chemistry
Volume250
Issue number9
StatePublished - 1975

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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