Xylulose reductase

Lane AB (1985) On the nature of L-xylulose reductase deficiency in essential pentosuria. Biochem Genet 23 61-72... 

Essential pentosuria is a metabolic condition characterized by deficiency in the major isoform of L-xylulose reductases in human tissues homozygote individuals have only a residual activity of the enz)me [40], and thus excrete large concentrations of L-xylulose into urine. A minimum estimate of the Irequency of the pentosuria allele in an Ashkenazi-Jewish population is 0.0127 [41]. This metabolic disease is absolutely harmless, especially because the specific and selective anal)Tical techniques in use in modem diabetology should prevent a false positive diagnosis in essential pentosuria patients. 

L-Xylulose reductase (xylitol dehydrogenase) is deficient in essential pentosuria. L-Xylulose (a pentose) appears in the urine and gives a positive reducing-sugar test. The condition is benign. 

This is a harmless inborn error caused by a deficiency of l-xylulose reductase, an enzyme involved in the glucuronic acid pathway. 

Carbone V, Ishikura S, Hara A et al (2005) Structure-based discovery of human L-xylulose reductase inhibitors from database screening and molecular docking. Bioorg Med Chem... 

Occurrence. The ketopentose 14 (L-xylulose) is found in the urine of many cases of pentosuria.62 It was also detected in the serum of adult-onset diabetics.63 Essential pentosuria is the result of a partial deficiency of L-xylulose reductase.64... 

A hydrogenase from Alcaligenes entrophus coupled with a xylulose reductase from a yeast, have been used to produce xylitol from D-xylulose. ... 

D-Xylose Isomerases.—An enzymic method that employs a commercial preparation of L-iditol dehydrogenase containing D-xylulose reductase activity has been reported for the assay of o-xylose isomerase. ... 

Recombinant Saccharomyees cerevisiae, able to ferment the pentoses D-xylose and L-arabinose, was modified for improved fermentation rates and yields. Pentose fermentation is relevant when low cost raw materials such as plant hydrolysates are fermented to ethanol. The two most widespread pentose sugars in our biosphere are D-xylose and L-arabinose. S. cerevisiae is unable to ferment pentoses but has been engineered to do so however rates and yields are low. The imbalance of redox cofactors (excess NADP and NADH are produced) is considered a major limiting factor. For the L-arabinose fermentation we identified an NADH-dependent L-xylulose reductase replacing the previously known NADPH-dependent enzyme. For D-xylose fermentation we introduced an NADP-dependent glyceraldehyde 3-phospate dehydrogenase to regenerate NADPH. 

Figure I. The fungal and bacterial pathways for D-xylose and L-arabinose catabolism. All pathways have in common that D-xylulose 5-phosphate is produced. The enzymes in the bacterial pathways are xylose isomerase and xylulokinase for the D-xylose pathway and L-arabinose isomerase, ribulokinase and L-ribulosephosphate 4-epimerase for the L-arabinose pathway. The fungal D-xylose pathway has the enzymes aldose reductase, xylitol dehydrogenase and xylulokinase. The enzymes in the L-arabinose pathways ofmold and yeast are aldose reductase, L-arabinitol 4-dehydrogenase, L-xylulose reductase, xylitol dehydrogenase and xylulokinase. The differences between the mold and yeast pathway are in the cofactor requirements.

Different pathways are available in nature for metabolism of arabinose and xylose which are converted to xylulose 5-phosphate (intermediate com-poimd) to enter the pentose phosphate pathway as shown in Figure 10.5. In yeasts, xylose is first reduced by xylose reductase to xylitol, which in turn is oxidized to xylulose by xylitol dehydrogenase. In bacteria and some anaerobic fungi, xylose isomerase is responsible for direct conversion of xylose to xylulose. Xylulose is finally phosphorylated to xylulose-5-phos-phate by xylulokinase. In fungi, L-arabinose is reduced to L-arabitol (by arabinose reductase), L-xylulose (by arabitol dehydrogenase), xylitol (by L-xylulose reductase). Xylitol is finally converted to xylulose (by xylitol dehydrogenase), whose activity is also part of xylose utilization pathways. In bacteria, L-arabinose is converted to L-ribulose (by L-arabinose isomerase), L-ribulose-5-P (by L-ribulokinase) and finally D-xylulose-5-P (by L-ribulose-5-P 4-epimerase) (Bettiga et al., 2008). 

The clinical effects of an inborn error of metabolism, and the time course of any disease caused, depend on the nature of the defect and, to some extent, the external environment. Absence of L-xylulose reductase causes accumulation of L-xylulose which is excreted in the urine [1]. Pentosuria is, as far 21s is known, a completely harmless biochemical abnormality, L-xylulose being non-toxic and xylitol not being an essential... 

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