Possible role of the NADH-fumarate reductase in superoxide anion and hydrogen peroxide production in Trypanosoma brucei

Mitochondrial membranes from Trypanosoma brucei procyclic trypomastigotes generated superoxide anion and hydrogen peroxide in a 2:1 ratio when supplemented with NADH. Fumarate inhibited hydrogen peroxide formation ( K i = 16 μM) with the same affinity as it stimulated NADH-fumarate reductase activity. Superoxide anion production was also 65% inhibited by fumarate ( K i = 20 μM). The K M for NADH of the NADH-fumarate reductase (60 μM) was also similar to that for hydrogen peroxide generation in the absence of fumarate (30 μM). These results suggest that the NADH-fumarate reductase is involved as a source for free radical generation in T. brucei mitochondria.