• We previously demonstrated in streptozotocin-induced diabetic mice that deficiency or inhibition of aldose reductase (AR) caused significant dephosphorylation of hepatic transcriptional factor PPAR α , leading to its activation and significant reductions in serum lipid levels. (hindawi.com)
  • These results indicated that aldose reductase may be related to radiation-induced lung epithelial cells EMT, and that inhibition of aldose reductase might be a promising treatment for RIPF. (bvsalud.org)
  • citation needed] In Drosophila, CG6084 encoded a highly conserved protein of human Aldo-keto reductase 1B. (wikipedia.org)
  • Aldose reductase may be considered a prototypical enzyme of the aldo-keto reductase enzyme superfamily. (wikipedia.org)
  • The aldo-keto reductase (AKR) superfamily includes a huge collection of NAD(P)H-dependent oxidoreductases that carry out a variety of redox reactions essential for biosynthesis, detoxification, and intermediary metabolism. (bvsalud.org)
  • In enzymology, aldose reductase (or aldehyde reductase) (EC 1.1.1.21) is a cytosolic NADPH-dependent oxidoreductase that catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides. (wikipedia.org)
  • The polyol pathway is a glucose metabolic shunt that is defined by two enzymatic reactions catalyzed by aldose reductase (AR, AKR1B1, EC1.1.1.21) and sorbitol dehydrogenase (SDH, EC1.1.1.14), respectively [ 1 , 2 ]. (hindawi.com)
  • The AvAKR preferred cytoplasmic localization and shared similarities with the known plant AKRs, keeping the majority of the conserved active-site residues in the AKR superfamily enzymes. (bvsalud.org)
  • Aldose reductase (AR) is a monomer enzyme in the polyglycolic metabolic pathway and belongs to the aldo-keno reductase protein superfamily. (bvsalud.org)
  • Thus, aldose reductase provides a critical metabolic checkpoint in the global inflammatory response. (wikipedia.org)
  • The enzyme comprises 315 amino acid residues and folds into a β/α-barrel structural motif composed of eight parallel β strands. (wikipedia.org)
  • There exist three residues in the enzyme within a suitable distance of the C-4 that could be potential proton donors: Tyr-48, His-110 and Cys-298. (wikipedia.org)
  • It is primarily known for catalyzing the reduction of glucose to sorbitol, the first step in polyol pathway of glucose metabolism. (wikipedia.org)
  • Aldose reductase catalyzes the NADPH-dependent conversion of glucose to sorbitol, the first step in polyol pathway of glucose metabolism. (wikipedia.org)
  • Thus, the polyol pathway results in conversion of glucose to fructose with stoichiometric utilization of NADPH and production of NADH. (wikipedia.org)
  • glucose + NADPH + H+ ⇌ {\displaystyle \rightleftharpoons } sorbitol + NADP+ Galactose is also a substrate for the polyol pathway, but the corresponding keto sugar is not produced because sorbitol dehydrogenase is incapable of oxidizing galactitol. (wikipedia.org)
  • The main pathway from glucose to fructose (glycolysis) involves phosphorylation of glucose by hexokinase to form glucose 6-phosphate, followed by isomerization to fructose 6-phosphate and hydrolysis of the phosphate, but the sorbitol pathway is useful because it does not require the input of energy in the form of ATP: Seminal vesicles: Fructose produced from sorbitol is used by the sperm cells. (wikipedia.org)
  • Nevertheless, aldose reductase can catalyze the reduction of galactose to galactitol galactose + NADPH + H+ ⇌ {\displaystyle \rightleftharpoons } galactitol + NADP+ The aldose reductase reaction, in particular the sorbitol produced, is important for the function of various organs in the body. (wikipedia.org)
  • The reaction mechanism of aldose reductase in the direction of aldehyde reduction follows a sequential ordered path where NADPH binds, followed by the substrate. (wikipedia.org)
  • Kinetic studies have shown that reorientation of this loop to permit release of NADP+ appears to represent the rate-limiting step in the direction of aldehyde reduction. (wikipedia.org)
  • The enzyme facilitated the NADPH-dependent reduction of various carbonyl substrates, including benzaldehyde and sugars, proclaiming a broad spectrum range. (bvsalud.org)
  • Our data suggest that inhibition of AR in the T2DM db/db mice led to significant activation in hepatic PPAR α and significant reductions in serum triglycerides (TG) and hepatic TG, suggesting that under hyperglycemia, AR/the polyol pathway might be greatly upregulated to contribute significantly to the hepatic regulation of TG metabolism and the development of nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver disease (NAFLD). (hindawi.com)
  • AR/the polyol pathway have been demonstrated to play important roles in the development and progression of diabetic complications in a number of tissues including kidney, retina, lens, and peripheral neuron tissues [ 3 - 5 ]. (hindawi.com)
  • Akr1b3 in mice), a key enzyme of the polyol pathway, mediates lipid accumulation in the murine heart and liver. (uky.edu)
  • The study objective was to explore potential roles for AKR1B1/Akr1b3 in the pathogenesis of obesity and its complications. (uky.edu)
  • Methods: The study employed mice treated with an inhibitor of aldose reductase or mice devoid of Akr1b3 were used to determine their response to a high-fat diet. (uky.edu)
  • The study used subcutaneous adipose tissue-derived adipocytes to investigate mechanisms by which AKR1B1/Akr1b3 promotes diet-induced obesity. (uky.edu)
  • Conclusions: AKR1B1/Akr1b3 modulation of senescence in subcutaneous adipose tissue contributes to aberrant metabolic responses to high-fat feeding. (uky.edu)
  • Aldose reductase catalyzes the NADPH-dependent conversion of glucose to sorbitol, the first step in polyol pathway of glucose metabolism. (wikipedia.org)
  • Thus, the polyol pathway results in conversion of glucose to fructose with stoichiometric utilization of NADPH and production of NADH. (wikipedia.org)
  • glucose + NADPH + H+ ⇌ {\displaystyle \rightleftharpoons } sorbitol + NADP+ Galactose is also a substrate for the polyol pathway, but the corresponding keto sugar is not produced because sorbitol dehydrogenase is incapable of oxidizing galactitol. (wikipedia.org)
  • Nevertheless, aldose reductase can catalyze the reduction of galactose to galactitol galactose + NADPH + H+ ⇌ {\displaystyle \rightleftharpoons } galactitol + NADP+ The aldose reductase reaction, in particular the sorbitol produced, is important for the function of various organs in the body. (wikipedia.org)
  • The reaction mechanism of aldose reductase in the direction of aldehyde reduction follows a sequential ordered path where NADPH binds, followed by the substrate. (wikipedia.org)
  • Results: Increased expression of aldose reductase and senescence in the adipose tissue of humans and mice with obesity were demonstrated. (uky.edu)
  • Kinetic studies have shown that reorientation of this loop to permit release of NADP+ appears to represent the rate-limiting step in the direction of aldehyde reduction. (wikipedia.org)
  • The aldose reductase (AR) gene, a rate-limiting enzyme of the polyol pathway, has been investigated as a candidate gene in determining susceptibility to diabetic microangiopathy. (nih.gov)