Glucuronic acid glucuronate epimerization

Feingold, D.S., Neufeld, E.F., and Hassid, W.Z. (1960) The 4-epimerization and decarboxylation of uridine diphosphate d-glucuronic acid by extracts from Phaseolus aureus seedlings. JBiol.Chem. 235 910-913. 

It is important to note that the foregoing, biosynthetic-polymer modification is usually incomplete. In fact, only a fraction of the heparin precursor undergoes all of the transformations shown in Scheme 1. However, as the product of each enzymic reaction constitutes the specific substrate for the succeeding enzyme, the biosynthesis of heparin is not a random process. Thus, sulfation occurs preferentially in those regions of the chain where the amino sugar residues have been N-deacetylated and N-sulfated, and where D-glucuronic has been epimerized to L-iduronic acid.20... 

L-lduronic acid synthesis Synthesis of L-iduronic acid residues occurs after D-glucuronic acid has been incorporated into the carbohydrate chain. Uronosyl 5-epimerase causes epimerization of the D- to the L-sugar. 

Aldaric acids or their derivatives undergo ready epimerization in pyridine. Alkaline treatment of 4-O-methyl-D-glucuronic acid in the presence of air affords 4-O-methyl-D-glucaric and -D-mannaric acids as well as lower O-methylaldaric acids.262 The two diastereo-isomeric 3-deoxy-2-C-(hydroxymethyl)pentaric acids obtained from... 

At a relative humidity of 80%, the sodium salt of pig-mucosal heparin shows a fiber repeat of 1.65 nm, with a triclinic unit-cell containing one chain. The sodium salt of macromolecular heparin from rat skin, at 78% r.h., showed a repeat of 1.73 nm, and crystallized in an orthorhombic unit-cell. After 24 hours at 84% r.h., the repeat changed to 1.65 nm, the pattern corresponding to that of pig-mucosal heparin. The stereochemistry of the chain in terms of the chain repeat and , i/r maps was discussed. It was suggested that the chemical formula for heparin is poly[(l— 4)-/3-D-GlcpA-(l— 4)- -d-GlcNAcp], and a scheme of 5-epimerization of /3-D-glucuronic acid to a-L-iduronic acid was discussed. 

Other modification reactions include N-sulfation of the glucosamine residue, formation of iduronate by epimerization of glucuronate residues, and O-sulfation of C(, on glucosamine and C2 on iduronic acid. Epimerization may be linked to O-sulfation of iduronic acid, since experimental elimination of PAPS blocks the epimerization reaction. O-sulfation may stabilize the iduronic configuration around C5, favoring its formation. 

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