The high levels of both enzymes of glutathione synthesis found in the infant human lens rapidly reached lower levels by age 10, and thereafter the rate of decrease diminished. Glutathione synthetase activity in the 6 month old lens was six-fold (units/g lens), four-fold (units/mg soluble protein) and two-fold (units/lens) higher than that in the 83 year old, clear human lens. gamma-Glutamylcysteine synthetase activity in the 6 month old lens was sixteen-fold (units/g lens), ten-fold (units/mg soluble protein) and six-fold (units/lens) higher than that in the 83 year old, clear human lens. When lenses from the young adult beagle, rabbit, bovine, and humans are compared, glutathione synthetase activity (units/g lens) varies by about two-fold. gamma-Glutamylcysteine synthetase activity (units/g lens) is quite similar in the first three species, whereas the enzyme activity is more than a magnitude less in young adult human lenses, and becomes much less with increasing age and in a high proportion of life-support system organ donors. The enzyme activity was undetectable in a few of the latter lenses. Loss of activity was not due to increased susceptibility to heat denaturation. The low levels of the enzyme, and total loss in some situations, suggest that gamma-glutamylcysteine synthetase may be an Achilles' Heel of human lens metabolism.
Lenses from 42 eye bank eyes were assayed for glutathione peroxidase and glutathione reductase activities. The activity of glutathione peroxidase, when considered as a function of age, was lowest in the neonate lens, increasing with age to reach maximal values in young adult lenses, and thereafter progressively decreasing with ages greater than 40 years. Glutathione reductase activity was little affected by age when expressed as activity per lens, per gram lens or per mg soluble protein, indicating that activity of this enzyme did not increase with lens size as would a representative lenticular protein. However, the activity of this enzyme per gram lens was among the highest of any species yet examined.
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