DCXR
L-xylulose reductase (EC 1.1.1.10) (XR) (Carbonyl reductase II) (Dicarbonyl/L-xylulose reductase) (Kidney dicarbonyl reductase) (kiDCR) (Short chain dehydrogenase/reductase family 20C member 1) (Sperm surface protein P34H) [SDR20C1]
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Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol. It also reduces highly reactive α-dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. Enzymatic properties of DCXR from yeast, fungi and mammalian tissue extracts are extensively studied. Deficiency of the DCXR gene causes a human clinical condition called pentosuria and low DCXR activity is implicated in age-related diseases including cancers, diabetes, and human male infertility. While mice provide a model to study clinical condition of these diseases, it is necessary to adopt a physiologically tractable model in which genetic manipulations can be readily achieved to allow the fast genetic analysis of an enzyme with multiple biological roles. Caenorhabditis elegans has been successfully utilized as a model to study DCXR. Here, we discuss the biochemical properties and significance of DCXR activity in various human diseases, and the utility of C. elegans as a research platform to investigate the molecular and cellular mechanism of the DCXR biology.
MeSH Terms
- Amino Acid Sequence
- Animals
- Carbohydrate Metabolism, Inborn Errors
- Humans
- Models, Molecular
- Molecular Sequence Data
- Sugar Alcohol Dehydrogenases
- Xylulose
Keywords
- AGE
- DC
- DCXR
- DEP
- Dicarbonyl/l-xylulose dehydrogenase
- Fertility
- Longevity
- Pentosuria
- RAGE
- SDR
- advanced glycation end-products
- dhs-21
- dicarbonyl/l-xylulose reductase
- diesel exhaust particles
- receptor for AGE
- short-chain dehydrogenase/reductase
- α-dicarbonyl compound
Dicarbonyl/L-xylulose reductase (DCXR) converts l-xylulose into xylitol, and reduces various α-dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. In this study, we identified DHS-21 as the only DCXR ortholog in Caenorhabditis elegans. The dhs-21 gene is expressed in various tissues including the intestine, gonadal sheath cells, uterine seam (utse) cells, the spermathecal-uterus (sp-ut) valve and on the plasma membrane of spermatids. Recombinant DHS-21 was shown to convert L-xylulose to xylitol using NADPH as a cofactor. Dhs-21 null mutants of C. elegans show defects in longevity, reproduction and egg-laying. Knock-down of daf-16 and elt-2 transcription factors affected dhs-21 expression. These results suggest that DHS-21 is a bona fide DCXR of C. elegans, essential for normal life span and reproduction.
MeSH Terms
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Biocatalysis
- Blotting, Western
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Female
- Green Fluorescent Proteins
- Kinetics
- Longevity
- Male
- Microscopy, Fluorescence
- Molecular Sequence Data
- Mutation
- NADP
- RNA Interference
- Recombinant Proteins
- Reproduction
- Sequence Homology, Amino Acid
- Sugar Alcohol Dehydrogenases
- Xylitol
- Xylulose