Oxidized Aldose Reductase:In VivoFactor, Notin VitroArtifact

摘要: Characterization of aldose reductase purified from human placenta confirms that activation, as first analyzed in detail for the bovine enzyme, also occurs humans. Routinely between 5 and 20% activity freshly exhibits kinetic properties insensitivity to inhibitors (ARIs) characteristic activated or oxidized enzyme form, determined using a sensitive Sorbinil titration assay. In confirmation previous studies, amount ratio aldehyde show wide patient variability, with accounting 30 95% total aldo-keto activity. The behavior described isolated tissues (e.g., biphasic Dixon plots ARI inhibition) can be reproduced exactly mixtures native recombinant is not restricted DL-glyceraldehyde. Measurement substrate (NADPH versus NADPD solvent (H2O D2O) deuterium isotope effects indicates ARI-resistant form altered manner perturbs relative rates steps along normal reaction pathway. These results suggest only level activity, but extent activation vivo, may an important factor determining susceptibility diabetic complications responsiveness therapy.