G6PD molecules devoid of catalytic activity are present in the nucleus of the rat lens.

The specific activity of glucoso-6-phosphate dehydrogenase (G6PD) in the rat lens declines as a function of animal age. G6PD activity could be found only in the cortex of the lens. Previous work showed that antibodies against the 'native' form of G6PD could not recognize any cross-reacting material (CRM) in the lens. It was speculated that this could be due either to disappearance of G6PD from the nucleus by degradation or by alterations of the molecules which resulted in the loss of their antigenic determinants. In order to investigate this question, an antibody was prepared against denatured G6PD. This antibody did not interact with 'native' (active) forms of the enzyme; it was shown, however, to recognize antigenically cross-reactive but catalytically inactive intact G6PD molecules in the nucleus of the lens. This finding suggests that altered enzyme molecules are at least partially denatured and accumulate in the lens without being further cleaved proteolytically.