Glutathione synthesis in evolution: an Achilles' heel of human and other old world simian lenses

The activities of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase, the two enzymes responsible for glutathione synthesis, were determined in adult lenses from representative species of eight mammalian orders. Lenses from Old World higher simians, including man, exhibited remarkably low gamma-GCS activity when compared to a prosimian and the other seven orders. In contrast, glutathione synthetase activity was comparable and relatively high in all orders. This, together with knowledge of its known lability and control mechanisms, suggests that gamma-GCS is a critical enzyme in the lens of the aging higher primate, whose very low and rate-limiting activity is a latent factor in the development of age-related cataract.