Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osmoregulation in inner medullary cells depends in part on cellular accumulation of sorbitol, the production of which from glucose is catalyzed by aldose reductase. To identify nephron segments that contain aldose reductase, we developed a fluorometric ultramicroassay to measure aldose reductase activity in microdissected nephron segments from collagenase-treated kidneys of Sprague-Dawley rats. DL-Glyceraldehyde (10 mM) was used as a substrate. Substantial aldose reductase activities were found in all three inner medullary renal tubule segments: thin descending limbs, thin ascending limbs, and inner medullary collecting ducts. Activity increased with depth into the inner medulla in all three segments. When aldose reductase activities were normalized by cell volume the activities in the three inner medullary segments were similar. Little or no aldose reductase activity was measured in glomeruli or any cortical or outer medullary nephron segment. Both proximal convoluted and proximal straight tubules were found to have a substantial capacity to reduce DL-glyceraldehyde, but the finding of greater reductase activity with D-glucuronate (10 mM) than with D-xylose (10 mM) indicated that the activity was due to aldehyde reductase. Sorbitol dehydrogenase (measured by a similar ultramicroassay method) was present in substantial amounts in proximal tubules, but not in inner medullary collecting ducts. The overall pattern of enzyme activities is consistent with the proposed osmoregulatory role for sorbitol in all three inner medullary renal tubule segments.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Aldose reductase activities in microdissected rat renal tubule segments. 249 37

Sorbitol dehydrogenase (SDH), a member of the medium-chain dehydrogenase/reductase protein family and the second enzyme of the polyol pathway of glucose metabolism, converts sorbitol to fructose strictly using NAD(+) as coenzyme. SDH is expressed almost ubiquitously in all mammalian tissues. The enzyme has attracted considerable interest due to its implication in the development of diabetic complications and thus its tertiary structure may facilitate the development of drugs for the treatment of diabetes sufferers. Modelling studies suggest that SDH is structurally homologous to mammalian alcohol dehydrogenase with respect to conserved zinc binding motif and a hydrophobic substrate-binding pocket. Recently, the three-dimensional (3-D) structure of a mammalian SDH was solved, and it was found that while the overall 3-D structures of SDH and alcohol dehydrogenase are similar, the zinc coordination in the active sites of the two enzymes is different. The available structural and biochemical information of SDH are currently being utilized in a structure-based approach to develop drugs for the treatment or prevention of the complications of diabetes. This review provides an overview of the recent advances in the structure, function and drug development fields of sorbitol dehydrogenase.
 ...
PMID:Sorbitol dehydrogenase: structure, function and ligand design. 1496 27