Activity of glutathione synthesis enzymes in human lens related to age

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.