Mechanism of "hypoglycemic" cataract formation in the rat lens. II. Further studies on the role of hexokinase instability.
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.
D000367:Age Factors; D000818:Animals; D002386:Cataract / Q000201:enzymology* / Q000209:etiology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004848:Epithelium / Q000201:enzymology; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D006593:Hexokinase; D005947:Glucose