The putative heparin-specific N-acetylglucosaminyl N-Deacetylase/N-sulfotransferase also occurs in non-heparin-producing cells.
N-Deacetylation and N-sulfation of N-acetylglucosamine of heparin and heparan sulfate are hypothesized to be mediated by different tissue-specific N-acetylglucosaminyl N-deacetylases/N-sulfotransferases, which in turn lead to the higher L-iduronic acid and sulfate content of heparin versus heparan sulfate. Furthermore, the putative heparin-specific N-acetylglucosaminyl N-deacetylase/N-sulfotransferase has been reported to require auxiliary proteins for its N-acetylglucosaminyl N-deacetylase activity in vivo based on its requirement of polycations in vitro. We have now found that cells derived from embryonic bovine trachea, a tissue that does not synthesize heparin, has a N-acetylglucosaminyl N-deacetylase/N-sulfotransferase, which has 95% amino acid sequence identity to the above enzyme postulated to be involved in the biosynthesis of heparin. Both enzymes also have very similar affinity for their substrates. The trachea enzyme does not require additional effectors for its N-acetylglucosaminyl N-deacetylase activity in vitro even though its biochemical characteristics are virtually the same as the enzyme previously isolated from cells of a heparin-producing mastocytoma tumor. The trachea enzyme, which is encoded by an abundant 4.6-kilobase mRNA, like mastocytoma cells, has 70% amino acid sequence identity with the corresponding enzyme from rat liver postulated to participate in the biosynthesis of heparan sulfate. Heparan sulfate synthesized by trachea cells has a higher content of sulfated iduronic acid than from other tissues. Together, the above results strongly suggest that the above enzymes from mastocytoma, liver, and trachea, per se, are not solely responsible for the selective tissue-specific synthesis of heparin or heparan sulfate; more likely cellular factors, additional enzymes, and availability of substrates in the Golgi lumen also play important roles in the differential synthesis of the above proteoglycans.
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118, USA.
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D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000581:Amidohydrolases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D017931:DNA Primers; D006493:Heparin / Q000378:metabolism*; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000201:enzymology
D000123:Acetyltransferases; D000581:Amidohydrolases; D017931:DNA Primers; D006493:Heparin; D006497:Heparan Sulfate; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D015238:Sulfotransferases; C113066:NDST2 protein, human