Sugar Epimerases

Eor shaping the 1,3-diaminocyclitol into its final configuration and into the actinamine structure, first an epimerization step has to invert the stereochemical placement of the 2-hydroxyl group, which is proposed to be catalyzed by the SpcD enzyme, being related to sugar epimerases second, the actinamine branch... 

Another group of sugar epimerases, which uses a metal cofactor instead of NADH/NAD+, takes an entirely different approach to epimerization. L-ribulose 5-phosphate 4-epimerase, which is involved in the bacterial metabolism of arabinose, performs a retro-aldol cleavage of a C-C bond to yield a metal-stabilized enolate of dihydroxyacetone and glycoaldehyde phosphate, similar to the reaction catalyzed by class II aldolases [77-79]. The glycoaldehyde phosphate is thought to rotate, such that addition of the enolate generates the isomeric product. 

Figure 7.1S. Two possible pathways for the stereoinversion of sugars by sugar epimerases utilizing the NADH/NAD+ cofactor.

Ketley, J. N., Schellenberg, K. A. Substrate stereochemical requirements in the reductive inactivation of uridine diphosphate galactose 4-epimerase by sugar and 5 -uridine monophosphate. Biochemistry 12, 315—320 (1973). 

Synthesis. The synthases are present at the endomembrane system of the cell and have been isolated on membrane fractions prepared from the cells (5,6). The nucleoside diphosphate sugars which are used by the synthases are formed in the cytoplasm, and usually the epimerases and the other enzymes (e.g., dehydrogenases and decarboxylases) which interconvert them are also soluble and probably occur in the cytoplasm (14). Nevertheless some epimerases are membrane bound and this may be important for the regulation of the synthases which use the different epimers in a heteropolysaccharide. This is especially significant because the availability of the donor compounds at the site of the transglycosylases (the synthases) is of obvious importance for control of the synthesis. The synthases are located at the lumen side of the membrane and the nucleoside diphosphate sugars must therefore cross the membrane in order to take part in the reaction. Modulation of this transport mechanism is an obvious point for the control not only for the rate of synthesis but for the type of synthesis which occurs in the particular lumen of the membrane system. Obviously the synthase cannot function unless the donor molecule is transported to its active site and the transporters may only be present at certain regions within the endomembrane system. It has been observed that when intact cells are fed radioactive monosaccharides which will form and label polysaccharides, these cannot always be found at all the membrane sites within the cell where the synthase activities are known to occur (15). A possible reason for this difference may be the selection of precursors by the transport mechanism. 

Conversion of the a-D-glucopyranosyl derivative (94a) into the a-D-galactopyranosyl ester (95a) was demonstrated370 in 1951 as the first example of an enzymic reaction of a sugar nucleotide. The enzyme that catalyzes this reaction, namely, uridine 5 -(a-D-glu-copyranosyl pyrophosphate) 4"-epimerase,371 is common in Nature. Purified preparations have been obtained from yeast,372 373 Escherichia coli 374-376 mung-bean seedlings,377 wheat germ,378 and animal tissues.244,379 380... 

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. 

Tphis review outlines the current knowledge of the enzyme mutarotase " (aldose-l-epimerase) and evaluates the evidence that it may have evolved from an origin in primitive bacteria into an important transport system for sugars in higher organisms. 

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