Identification and characterization of a novel human aldose reductase-like gene.
We have identified a novel human protein that is highly homologous to aldose reductase (AR). This protein, which we called ARL-1, consists of 316 amino acids, the same size as AR, and its amino acid sequence is 71% identical to that of AR. It is more closely related to the AR-like proteins such as mouse vas deferens protein, fibroblast growth factor-regulated protein, and Chinese hamster ovary reductase, with 81, 82, and 83%, respectively, of its amino acid sequence identical to the amino acid sequence of these proteins. The cDNA of ARL-1 was expressed in Escherichia coli to obtain recombinant protein for characterization of its enzymatic activities. For comparison, the cDNA of human AR was also expressed in E. coli and analyzed in parallel. These two enzymes differ in their pH optima and salt requirement, but they act on a similar spectrum of substrates. Similar to AR, ARL-1 can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. While AR mRNA is found in most tissues studied, ARL-1 is primarily expressed in the small intestines and in the colon, with a low level of its mRNA in the liver. The ability of ARL-1 to reduce various aldehydes and the locations of expression of this gene suggest that it may be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs. Interestingly, ARL-1 and AR are overexpressed in some liver cancers, but it is not clear if they contribute to the pathogenesis of this disease.
Cao
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Institute of Molecular Biology, University of Hong Kong, Pokfulam, Hong Kong.
Fan
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Chung
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D000328:Adult; D000449:Aldehyde Reductase / Q000235:genetics*; D000074408:Aldo-Keto Reductases; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D002712:Chlorides / Q000494:pharmacology; D003001:Cloning, Molecular; D015870:Gene Expression; D005796:Genes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016415:Sequence Alignment; D013379:Substrate Specificity; D013401:Sugar Alcohol Dehydrogenases / Q000235:genetics*; D013431:Sulfates / Q000494:pharmacology
D002712:Chlorides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013431:Sulfates; D013401:Sugar Alcohol Dehydrogenases; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase