“Coding” and “Decoding”: hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis

•Two major steps, “coding” and “decoding”, are involved in the biosynthesis of HS.•“Coding” is based on the distribution of sulfate moieties on the glucosamine.•“Code” is created by N-deacetylase/N-sulfotransferase, which has four isozymes.•C5-epimerase and O-sulfotransferases recognized the “Code”....

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Vydané v:Carbohydrate research Ročník 428; s. 1 - 7
Hlavní autori: Zhang, Xu, Wang, Fengshan, Sheng, Juzheng
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Netherlands Elsevier Ltd 16.06.2016
Predmet:
Animals
bioactive properties
Biocatalysis
biosynthesis
Biosynthesis mechanism
Biosynthetic Pathways
C5-epimerase
DNA
enzymes
glucosamine
Glucosamine - chemistry
Heparan sulfate
Heparitin Sulfate - biosynthesis
Heparitin Sulfate - chemistry
Humans
Isoenzymes - metabolism
isozymes
mammals
Molecular Structure
N-deacetylase/N-sulfotransferase
O-sulfotransferase
proteoglycans
sulfates
Sulfotransferases - metabolism
Heparan sulfate
C5-epimerase
N-deacetylase/N-sulfotransferase
O-sulfotransferase
Biosynthesis mechanism
ISSN:0008-6215, 1873-426X, 1873-426X
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Shrnutí:•Two major steps, “coding” and “decoding”, are involved in the biosynthesis of HS.•“Coding” is based on the distribution of sulfate moieties on the glucosamine.•“Code” is created by N-deacetylase/N-sulfotransferase, which has four isozymes.•C5-epimerase and O-sulfotransferases recognized the “Code”.•This mechanism regulates chemical structure and biological activity of HS. Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely “coding” and “decoding” steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The “coding” process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the “decoding” process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity.
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ISSN:0008-6215
1873-426X
1873-426X
DOI:10.1016/j.carres.2016.04.002