Organ- and species-specific properties of glucose-6-phosphate dehydrogenase and the effect of molsidomine

Glucose-6-phosphate dehydrogenase (G-6-PDH) is the key enzyme of the pentose phosphate cycle and therefore regulates the synthesis of the nucleic acid constituent ribose-5-phosphate. At the same time the enzyme is coupled to the synthesis of reduced glutathione (GSH) which detoxifies electrophilic molecules (radicals) in the organism. Activity and stability of G-6-PDH and the influence of SIN 1--the active metabolite of molsidomine (Corvaton)--dithiothreitol (DTT) and NADP on these parameters were studied in enzyme preparations from different organs of the rat (liver, ethmoturbinates, blood) and from blood of mouse, guinea pig, rabbit, dog and man. The highest activity of G-6-PDH was measured in rat ethmoturbinates (69.26 +/- 5.91 mU/mg protein/min), the lowest in human blood (2.99 +/- 0.18 mU/mg protein/min). G-6-PDH of rat ethmoturbinates and of rat and dog blood was unstable and nearly completely inhibited by SIN 1. The enzyme of rat liver and of human, mouse, guinea pig and rabbit blood was stable and not influenced by SIN 1. These organ-and species-specific findings are discussed with respect to the toxicological actions of SIN 1.(ABSTRACT TRUNCATED AT 250 WORDS)