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 (Ki = 16 microM) with the same affinity as it stimulated NADH-fumarate reductase activity. Superoxide anion production was also 65% inhibited by fumarate (Ki = 20 microM). The KM for NADH of the NADH-fumarate reductase (60 microM) was also similar to that for hydrogen peroxide generation in the absence of fumarate (30 microM). These results suggest that the NADH-fumarate reductase is involved as a source for free radical generation in T. brucei mitochondria.