Sorbitol Polyol Dehydrogenase

Different preparative procedures have been shown to yield protein fractions which are able to catalyze different types of reactions with respect to their requirement of either NAD or NADP as coenzymes [cf. Eqs. (19), (20), and (21)]. In sera of mice poisoned by carbon tetrachloride we found polyol dehydrogenases catalyzing the oxidation of the following polyols (a) with NAD sorbitol, ribitol, mannitol (b) with NADP sorbitol, ribitol. Erythritol and mt/o-inositol were not attacked at all. Figures 8 and 9 show the results of these determinations performed at pH 9.6. In the NAD system sorbitol and ribitol are oxidized at exactly the same rate, while in the NADP system ribitol does not reach the rate of sorbitol. The ratio NAD NADP for sorbitol is calculated to be 4.20 and for ribitol 5.50. Mannitol is oxidized at 23% of the rate of sorbitol. 

Fic. 8. NAD polyol dehydrogenase in sera of CCl4-poisoned mice sorbitol, ribitol, and mannitol oxidation (pH 9.6 polyols as substrates). 

The role that polyol dehydrogenases play in metabolism has scarcely been elucidated. Approaches were made by investigating the metabolic fate of C14-labeled sorbitol after oral and parenteral administration. It has been found that in normal animals C1402 was expired following the administration of labeled sorbitol, while eviscerated, liverless subjects showed no C1402 expiration under these conditions, thus confirming... 

IDH) from Candida utilis, also known as sorbitol or polyol dehydrogenase[35, 85. Reduction of the ketone occurs to give the alcohol with (S)-stereochemistry. The corresponding (R)-alcohol was obtained by non-stereoselective reduction of the ketone with NaBH(OAc)3 and the (S)-epimer was selectively removed by IDH-catalyzed oxidation. L-Xylose and 2-deoxy-D-orobino-hexose were synthesized by each of these two processes, respectively. 

Polyol dehydrogenase. Sorbitol dehydrogenase. L-iditol + NAD(+) = L-sorbose + NADH. 

Another polyol dehydrogenase has been found in seminal gland. This requires TPN and converts sorbitol to glucose (XXVII). The formation of an aldose contrasts with the formation of ketose by the other polyol dehydrogenases. The combined action of the TPN and DPN enzymes concerned with sorbitol metabolism may account for the accumulation of fructose by seminal vesicles. 

In clinical chemistry however, these systems have not been differentiated as yet. Since the oxidation of an alcohol corresponds to the reduction of a ketose or an aldose, the designations ketose reductase and aldose reductase, respectively, were suggested (H4, W14). In this paper however, the enzyme or enzyme system will be named polyol or sorbitol dehydrogenase (SDH), although the latter expression does not characterize exacdy the enzyme s function in a general biochemical sense. But sorbitol or fructose have been commonly used as substrates in clinical chemical investigations. 

Schematic of the polyol pathway showing the NADPH-dependent reduction of open chain D-glucose to sorbitol, which is catalyzed by ALR2. This step is followed by the NAD+-dependent oxidation of sorbitol by sorbitol dehydrogenase to yield D-fructose.

A random urine sample can be used for the analysis of polyols. TALDO and RPI deficiencies, as well as galactosaemia and presumably sorbitol dehydrogenase deficiency, can be diagnosed using urine. The samples are stored frozen. Repeated freeze-thawing does not influence the concentrations of the polyols. 

Figure 6.5. Compatibility of organic osmolytes with enzyme function. (Upper panel) Pyruvate kinase of the marine crab Pachygrapsus crassipes. The effects of KC1 and NaCI and several organic solutes on the Km of phosphoenol pyruvate (PEP) (modified after Bowlus and Somero, 1979). (Middle panel) Malate dehydrogenase of the mangrove (Rhizophora mangle). Effects of NaCI and three organic osmolytes (the amino acid proline and the polyols pinitol and OMMI) on catalytic activity (modified after Sommer et al., 1990). (Bottom panel) Effects of NaCI and four osmolytes found in mammalian kidney (urea, glycine betaine, sorbitol, and inositol) on the Km of uric acid of uricase (modified after Yancey, 1992). (Figure modified after Somero and Yancey, 1997.)...

Excess glucose can enter the polyol pathway, where it is reduced to sorbitol (by aldose reductase and the reductant NADPH). Sorbitol dehydrogenase will oxidise sorbitol to fructose, which also produces NADH from NAD+. Hexokinase will return fructose to the glycolysis pathway by phosphorylating it to fructose-6-phosphate. However, in uncontrolled diabetics with high blood glucose, the production of sorbitol is favoured. 

Reductions catalyzed by glycerol dehydrogenase, sorbitol dehydrogenase, mannitol dehydrogenase, and aldose reductases formation of polyols from carbohydrates. 

The polyol pathway consists of two enzymes, AR and sorbitol dehydrogenase. AR has a rather broad substrate specificity for sugars and a fairly high Km for glucose.These two enzymes catalyze the following reactions ... 

---