Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Cataract formation in streptozotocin-induced diabetes in rats was reduced by approximately 85% when a diet rich in maize oil (300 g/kg diet) (fat diet) was given, thus confirming results of earlier studies. However, the concentration of sorbitol in the lens of diabetic animals remained high, the values for diabetic rats given the standard diet and the fat died being 65 and 40 mumol/g protein respectively. 2. With the standard diet, the fatty acid profile of the triglycerides of the epididymal fat pads was characterized by a greater relative proportion of saturated fatty acids for the diabetic animals compared to that for the normal animals. The fat diet moderated the tendency towards saturation in the diabetic animals. 3. The fat diet had other effects on the diabetic animals; these included a reduced mortality rate, increased body-weight, a decrease in the daily water intake, and in the daily urinary excretion of glucose and urea. 4. In the diabetic animals the fat diet had no effect on the specific activities in the liver of hexokinase (EC 2.7.1.1), glucokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40). However, the specific activity of glucose-6-phosphatase (EC 3.1.3.9) was reduced, while that of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was increased. The NAD+:NADH ratio, as calculated from liver pyruvate and lactate concentrations, tended to increase. 5. The results suggested that the fat diet moderated the long-term metabolic effects of diabetes.
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PMID:The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats. 13 11

In Part I1 of this study, the thermolability of lens hexokinase was implicated in the development of an experimental "hypoglycemic" cataract. After eight hours of glucose deprivation, there is a precipitous loss of lens hexokinase. This occurs approximately nine hours prior to the disorganization of the other enzymatic steps in glycolysis. Epithelial hexokinase, as an immediate response to glucose deficiency, shifts from the soluble to the insoluble phase. There is no such shift in the cortex-nucleus where only soluble hexokinase is found. After eight hours of glucose deprivation, both soluble and insoluble hexokinases throughout the lens undergo rapid deactivations. During the first eight hours of glucose deprivation the loss of lenticular ATP and K+ and the gain in wet weight can be reversed by restoring normal glucose levels; beyond eight hours the changes are irreversible. During the period of reversibility, hexokinase activity levels are normal; during the period of irreversibility hexokinase activity is 10 to 20 per cent of normal. Of the substances tested (mannose, galactose, fructose, glutamine, adenosine) only mannose could sustain the lens in the absnece of glucose. Neither endogenous free glucose nor glycogen could sustain the lens in the face of glucose deprivation. There appear to be no alternative exogenous or endogenous energy yielding substrates. The younger the animal, the more susceptible is its lens to glucose deprivation. This most certainly is a reflection of the increased susceptibility of younger lenses to osmotic stress, since lenses in each age group manifested similar changes in hexokinase activity, ATP, Na+, and K+ level.
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PMID:Mechanism of "hypoglycemic" cataract formation in the rat lens. II. Further studies on the role of hexokinase instability. 93 98

Lenses from 100 gram albino rats remain clear and possess normal levels of Na+, K+, ATP, and hexokinase activity for 20 hours incubated in medium containing 12 mM glucose. Below 2.0 mM glucose, a cataract forms and there is an abrupt rise in lens Na+ and wet weight, a fall in lens K+, ATP, and hexokinase activity. The cataract is a thin lamellar opacity involving the anterior and posterior surfaces of the lens. If the lens is deprived of glucose for 48 hours, a nuclear cataract forms; the cortex between the superficial lamellar opacity and the nucleus being clear. This experimental cataract bears a striking resemblance to the hypoglycemic cataract seen in children. The thermal deactivation of hexokinase follows rapidly upon the depletion of its substrates (ATP and glucose) and is a primary factor leading to cataract formation. This was established by incubating the lens with 2-deoxyglucose, a competitive inhibitor of lens hexokinase. This compound blocks the entry of glucose into the glycolytic sequence. The cataract formed in its presence is identical morphologically and biochemically to that observed in a glucose-free medium. The effects of 2-deoxyglucose are prevented by increasing the glucose level; this rules out a direct toxic influence of 2-deoxyglucose and further supports the primary role of hexokinase thermolability in the etiology of this experimental cataract. This in vitro system appears to be an excellent experimental model for the study of the human hypoglycemic cataract.
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PMID:Mechanism of "hypoglycemic" cataract formation in the rat lens. I. The role of hexokinase instability. 118 8

Reviewed are (1) the biochemical basis and pathophysiology of diabetic complications and (2) the structure-activity relationships, pharmacology, pharmacokinetics, clinical trials, and adverse effects of aldose reductase inhibitors (ARIs). ARIs are a new class of drugs potentially useful in preventing diabetic complications, the most widely studied of which have been cataracts and neuropathy. ARIs inhibit aldose reductase, the first, rate-limiting enzyme in the polyol metabolic pathway. In nonphysiological hyperglycemia the activity of hexokinase becomes saturated while that of aldose reductase is enhanced, resulting in intracellular accumulation of sorbitol. Because sorbitol does not readily penetrate the cell membrane it can persist within cells, which may lead to diabetic complications. ARIs are a class of structurally dissimilar compounds that include carboxylic acid derivatives, flavonoids, and spirohydantoins. The major pharmacologic action of an ARI involves competitive binding to aldose reductase and consequent blocking of sorbitol production. ARIs delay cataract formation in animals, but the role of aldose reductase in cataract formation in human diabetics has not been established. The adverse effects of ARIs include hypersensitivity reactions. Although the polyol pathway may not be solely responsible for diabetic complications, studies suggest that therapy with ARIs could be beneficial. Further research is needed to determine the long-term impact and adverse effects of ARIs in the treatment of diabetic complications.
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PMID:Potential use of aldose reductase inhibitors to prevent diabetic complications. 211 49

Assay of the activities of hexokinase, phosphofructokinase, and pyruvate kinase showed that the first two declined in aging human lens cortex and all three enzymes retained constant activities in the epithelium throughout life. Moreover, both clear and cataractous aging lenses contained the same enzyme activities. ATP contents in cataracts, however, were lower than in clear lenses; in fact, after incubation at 37.5 degrees C in isotonic (290 to 300 mOsm), glucose-containing media, ATP was rapidly lost from cataracts (but not from clear lenses), suggesting excessive ATP expenditure in cataracts for osmotic balance. Cataracts incubated in media containing either glucose-6-phosphate or fructose-1, 6-diphosphate produced significantly higher ATP than with glucose in the media, indicating that glucose metabolism in human senile cataracts could be supplemented with hexose phosphates. Fructose-1, 6-diphosphate appeared to be more efficient than glucose-6-phosphate in preventing lens swelling during incubation.
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PMID:Supplementing glucose metabolism in human senile cataracts. 645 78

The distribution of glutathione reductase activity in concentric layers from the lens has been determined as a function of age for 16 species. Primate lenses have almost ten times the level of glutathione reductase found in other species. Comparison with the activity of hexokinase revealed that this is not due to a higher overall rate of metabolism in these lenses. By contrast, the higher activity found in bird and fish lenses reflects a higher metabolic activity in these tissues. In all species, a gradient of activity was observed with the highest specific activity in the outermost cortical fibres, decreasing to virtually no activity in the inner parts of the tissue. No alterations were found in this gradient with increasing age, other than an increase in the amount of nuclear tissue essentially devoid of activity. The maximum activity in the outer cortical fibres was the same, regardless of the age of the lens. The time taken, in different species, for the specific activity to decrease by half, was estimated from the rate of protein accumulation. This time was found to vary from a few days to several years, indicating that the decrease in activity is not due to ageing but rather, it is related to the maturation of fibre cells. These observations are discussed in terms of current concepts of lens ageing and cataract formation.
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PMID:Ageing of glutathione reductase in the lens. 783 1

A clinico-biochemical study indicated that the beta-blocker DL-propranolol may affect human lens epithelial hexokinase (HK) activity. In that study five key enzymes were analysed in 192 freshly excised human lens epithelia obtained during cataract surgery. In a large number of patients the epithelial HK was found to be inactive. Medical records of these patients showed widespread use of the drug DL-propranolol. In vitro experiments demonstrated a direct inhibitory effect of the drug on human lens HK activity. Lens refractive function was monitored during long term bovine lens culture experiments in which the potential cataractogenic agent was added to the culture media. DL-propranolol in a concentration of 0.1 mM reduced HK activity in bovine lens epithelium after 72 hr in organ culture and disrupted lens light focusing ability after 250 hr of incubation. Kinetic studies of HK inhibition suggested a competitive inhibitory effect of the drug on the enzyme.
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PMID:DL-propranolol inhibits lens hexokinase activity and affects lens optics. 815 26

Royal College of Surgeons (RCS) rats have hereditary retinal degeneration in association with posterior subcapsular opacities. Cataract formation is thought to be correlated with an increase in lipid peroxidation products in the vitreous (Zigler and Hess, 1985). In order to examine the possibility that parallel changes in enzyme activity are occurring within the lens, we analysed the activity of four key enzymes and the crystallin protein profile. We compared RCS rat lenses at three different stages of cataract formation to clear lenses of the nonpigmented RCS rat, lenses from pigmented RCS rat and to normal (Fisher) rat. Our data shows that concomitant with the appearance of the RCS cataract, the ratio of the crystallins beta 1, beta H and gamma to the total lens protein was reduced. The crystallin profile of a clear RCS lens was similar to that of a normal (Fisher) lens. No significant difference in the activity of the enzymes hexokinase and glucose-6-phosphate dehydrogenase (G6PD) was found among the lenses, however the activity of glutathione reductase and aldolase was reduced in the cataractous lenses.
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PMID:Enzyme activities and crystallin profiles of clear and cataractous lenses of the RCS rat. 840 88

Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications.
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PMID:Aldose reductase and its inhibition in the control of diabetic complications. 845 42

Ultraviolet (UV) radiation is one of the major risk factors of cataract (loss of eye-lens transparency). The influence of UVB radiation (300 nm; 100 microW cm-2) on the activity and apparent kinetic constants (Km and Vmax) of rat lens hexokinase (HK;EC 2.7.1.1), phosphofructokinase (PFK; EC 2.7.1.11), isocitrate dehydrogenase (ICDH; EC 1.1.1.41) and malate dehydrogenase (MDH; EC 1.1.1.37) of energy metabolism has been investigated by irradiating the lens homogenate of three- and 12-month-old rats. In the three-month-old group specific activities of HK and PFK are reduced by 56 and 43%, respectively, and there is no change in ICDH and MDH activities after a 24 h exposure. On the other hand, in the 12-month-old group the decreases are 72, 71, 24 and 16% for HK, PFK, ICDH and MDH, respectively. UVB irradiation increases the apparent Km of HK and PFK (in both age groups), whereas the Km of ICDH and MDH is not altered. While the decrease in Vmax of these enzymes due to UVB exposure is only marginal in three-month-old rats, it is more pronounced (significant) in 12-month-old rats. A similar decrease in enzyme activities of HK and PFK is also observed upon UVB exposure of the intact rat lens. The photoinduced changes in energy metabolism may in turn have a bearing on lens transparency, particularly at an older age.
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PMID:UVB irradiation alters the activities and kinetic properties of the enzymes of energy metabolism in rat lens during aging. 949 95


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