Activation of human erythrocyte, brain, aorta, muscle, and ocular tissue aldose reductase

Satish K. Srivastava, Naseem H. Ansari, Gregory A. Hair, Sanjay Awasthi, Ballabh Das

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Based upon kinetic, structural, and immunologic properties, we have demonstrated that human tissues have three major forms of aldo-keto reductases: aldose reductase (AR), and aldehyde reductases I (AR I) and II (AR II). The proposed subunit compositions are AR, alpha; AR I, alpha-beta; and AR II, delta. Only AR can effectively reduce glucose to sorbitol. The beta subunits in AR I alter the substrate specificity of AR and prevent conformational changes required for the activation of alpha subunits. Partially purified AR (by DE-52) from human erythrocytes expresses biphasic kinetics with glucose and glyceraldehyde. The enzyme can be activated with glucose + glucose-6-P + NADPH and is strongly inhibited by sorbinil, alrestatin, and quercetrin, and by ADP, 2,3DPG, 1,3DPG, and 3PGA. The activated enzyme expresses monophasic kinetics with substrates (Km glucose < 1 mmol/L) and is less susceptible to inhibition by synthetic AR inhibitors and phosphorylated intermediates. The enzyme from human brain, aorta, muscle, and ocular tissues was also activated under similar conditions. Erythrocyte enzyme was activated by incubation of blood with 30 to 50 mmol/L glucose. In diabetic subjects with blood sugar levels higher than 250 mg%, almost all the erythrocyte enzyme exists in the activated form. As demonstrated by enzyme-linked immunosorbent assay (ELISA), the increase in AR activity (in vivo and in vitro) was due to the activation of the enzyme and not to the de novo synthesis. In each case, the activation of the enzyme was confirmed by NADPH oxidation and the formation of proportionate amounts of sorbitol.

Original languageEnglish (US)
Pages (from-to)114-118
Number of pages5
Issue number4 SUPPL. 1
StatePublished - Apr 1986

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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