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61.
62.
Aldose reductase and aldehyde reductase belong to the aldo-keto reductase superfamily of enzymes whose members are responsible
for a wide variety of biological functions. Aldose reductase has been identified as the first enzyme involved in the polyol
pathway of glucose metabolism which converts glucose into sorbitol. Glucose over-utilization through the polyol pathway has
been linked to tissue-based pathologies associated with diabetes complications, which make the development of a potent aldose
reductase inhibitor an obvious and attractive strategy to prevent or delay the onset and progression of the complications.
Structural studies of aldose reductase and the homologous aldehyde reductase in complex with inhibitor were carried out to
explain the difference in the potency of enzyme inhibition. The aim of this review is to provide a comprehensive summary of
previous studies to aid the development of aldose reductase inhibitors that may have less toxicity problems than the currently
available ones.
Received 4 December 2006; received after revision 12 February 2007; accepted 20 April 2007 相似文献
63.
Dina C Meyre D Gallina S Durand E Körner A Jacobson P Carlsson LM Kiess W Vatin V Lecoeur C Delplanque J Vaillant E Pattou F Ruiz J Weill J Levy-Marchal C Horber F Potoczna N Hercberg S Le Stunff C Bougnères P Kovacs P Marre M Balkau B Cauchi S Chèvre JC Froguel P 《Nature genetics》2007,39(6):724-726
We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses. 相似文献
64.
tRNase Z: the end is not in sight 总被引:1,自引:0,他引:1
Although the enzyme tRNase Z has only recently been isolated, a plethora of data has already been acquired concerning the
enzyme. tRNase Z is the endonuclease that catalyzes the removal of the tRNA 3′ trailer, yielding the mature tRNA 3′ end ready
for CCA addition and aminoacylation. Another substrate cleaved by tRNase Z is the small chromogenic phosphodiester bis(p-nitrophenyl)phosphate (bpNPP), which is the smallest tRNase Z substrate known so far. Hitherto the biological function as
tRNA 3′-end processing enzyme has been shown only in one prokaryotic and one eukaryotic organism, respectively. This review
summarizes the present information concerning the two tRNase Z substrates pre-tRNA and bpNPP, as well as the metal requirements
of tRNase Z enzymes.
Received 29 March 2007; received after revision 15 May 2007; accepted 21 May 2007 相似文献
65.
Ras GTPases mediate a wide variety of cellular processes by converting a multitude of extracellular stimuli into specific biological responses including proliferation, differentiation and survival. In mammalian cells, three ras genes encode four Ras isoforms (H-Ras, K-Ras4A, K-Ras4B and N-Ras) that are highly homologous but functionally distinct. Differences between the isoforms, including their post-translational modifications and intracellular sorting, mean that Ras has emerged as an important model system of compartmentalised signalling and membrane biology. Ras isoforms in different subcellular locations are proposed to recruit distinct upstream and downstream accessory proteins and activate multiple signalling pathways. Here, we summarise data relating to isoform-specific signalling, its role in disease and the mechanisms promoting compartmentalised signalling. Further understanding of this field will reveal the role of Ras signalling in development, cellular homeostasis and cancer and may suggest new therapeutic approaches. 相似文献
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MUNCH-PETERSEN A 《Nature》1948,162(4118):537
70.