Thiol oxidation in the crystalline lens. I. The rate-limiting role of hexokinase in aging rat and human lenses.

Reduction of nonprotein disulfides required both glucose or glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide phosphate (NADP). However, hexokinase (HK) was found to be the rate-limiting step: the glucose-supported reduction rate was only 50% of that of G6P-supported activity. This disulfide-reducing activity seemed to decline in the aging lens. Further, the glucose-supported activity dropped substantially if HK was deactivated with diamide; the deactivation was partially reversible. HK activity in aging clear and cataractous human lenses had greatly diminished. This might explain the disproportionate decrease in glucose-supported reduction in the aging lens. The components of the disulfide-reducing mechanism in human lens were reviewed and discussed.