Publications

• The sorbitol pathway in the human lens: aldose reductase and polyol dehydrogenase.

  Jedziniak J.A., Chylack L.T. Jr., Cheng H.M., Gillis M.K., Kalustian A.A., Tung W.H.

  The sorbitol pathway in human lenses is evaluated on the enzymic level. Adult lenses, normal and nondiabetic as well as diabetic cataracts, are found to contain limited levels of aldose reductase (AR) and high levels of polyol dehydrogenase (PD) relative to the animal lens. AR is confined primaril ... >> More

  The sorbitol pathway in human lenses is evaluated on the enzymic level. Adult lenses, normal and nondiabetic as well as diabetic cataracts, are found to contain limited levels of aldose reductase (AR) and high levels of polyol dehydrogenase (PD) relative to the animal lens. AR is confined primarily to the lens epithelium and is two to three times higher in juvenile lenses than in the adult lens. The level of AR in the epithelium of juvenile lenses is sufficient to cause significant osmotic stress. The Km of glucose of AR is roughly 200 mM, whereas the Km for NADPH is 0.06 mM. NADP inhibits human lens AR noncompetitively and has a Ki equivalent to the Km for NADPH. PD occurs in both the lens epithelium and cortex, remains persistently high with age, and decreases with increased cortical involvement. The Km of sorbitol for PD is 1.4 mM and for NAD is 0.06 mM. NADH (Ki 0.002 mM) competitively inhibits PD in the forward direction. PD purified 100-fold from diabetic and nondiabetic cataracts and normal lenses exhibit similar kinetic constants. PD has an extremely high Vmax in the fructose-to-sorbitol direction. The Km of fructose is 40 mM and for NADH is 0.02 mM. At high enough concentration, alrestatin also inhibits PD. The added activities of AR and PD in producing sorbitol and fructose in combination with decreased hexokinase with age may account for diabetic cataract formation in human lenses exposed to a high glucose stress. Nucleotide levels are reported for senile cataractous lenses. << Less

  Invest Ophthalmol Vis Sci 20:314-326(1981) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Crucial role of aldose reductase activity and plasma glucose level in sorbitol accumulation in erythrocytes from diabetic patients.

  Hamada Y., Kitoh R., Raskin P.

  Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue so ... >> More

  Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue sorbitol levels may be due to differences in the activity of aldose reductase, the enzyme that converts glucose to sorbitol. In this study, we isolated aldose reductase from erythrocytes of 31 diabetic patients and 6 nondiabetic control subjects, measured its activity, and compared it to simultaneously measured erythrocyte sorbitol levels. The activity of erythrocyte aldose reductase was increased in diabetic patients compared with control subjects (28.1 +/- 1.4 vs. 22.4 +/-1.7 nmol.min-1.g-1 Hb, P less than 0.05), but there was an approximately threefold variation in aldose reductase activity among diabetic patients. Erythrocyte aldose reductase activity and fasting plasma glucose levels significantly correlated with the erythrocyte sorbitol level in all individuals (r = 0.48, P less than 0.005 and r = 0.63, P less than 0.005, respectively). The sorbitol level was higher in patients with high aldose reductase activity than in those who had low enzyme activity for any given level of glycemia. The sorbitol production rate calculated from Km and Vmax values showed a better correlation with the erythrocyte sorbitol level (r = 0.80, P less than 0.005), and there was also a good correlation between the erythrocyte sorbitol level and the product of aldose reductase activity by plasma glucose level (r = 0.70, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) << Less

  Diabetes 40:1233-1240(1991) [PubMed] [EuropePMC]

• Purification of alditol: NADP oxidoreductase from human placenta.

  Clements R.S. Jr., Winegrad A.I.

  Biochem Biophys Res Commun 47:1473-1479(1972) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.