Inhibitors of the mitochondrial cytochrome b-c1 complex inhibit the cyanide-insensitive respiration of Trypanosoma brucei.
The cyanide-insensitive respiration of bloodstream trypomastigote forms of Trypanosoma brucei (75 +/- 8 nmol O2 min-1(mg protein)-1) is completely inhibited by the mitochondrial ubiquinone-like inhibitors 2-hydroxy-3-undecyl-1,4-naphthoquinone (UHNQ) and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT). The Ki values for UHDBT (30 nM) and UHNQ (2 microM) are much lower than the reported Ki for salicylhydroxamic acid (SHAM) (5 microM), a widely used inhibitor of the cyanide-insensitive oxidase. UHNQ also stimulated the glycerol-3-phosphate-dependent reduction of phenazine methosulfate, demonstrating that the site of UHNQ inhibition is on the terminal oxidase of the cyanide-insensitive respiration of T. brucei. These results suggest that a ubiquinone-like compound may act as an electron carrier between the two enzymatic components of the cyanide-insensitive glycerol-3-phosphate oxidase.
D000818:Animals; D003486:Cyanides / Q000494:pharmacology; D003573:Cytochrome b Group / Q000037:antagonists & inhibitors; D003575:Cytochromes c1 / Q000037:antagonists & inhibitors; D005993:Glycerolphosphate Dehydrogenase / Q000037:antagonists & inhibitors; D008928:Mitochondria / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
C025993:5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole; D003486:Cyanides; D003573:Cytochrome b Group; D009285:Naphthoquinones; D012457:Salicylamides; D013844:Thiazoles; C039344:2-hydroxy-3-undecyl-1,4-naphthoquinone; C005703:salicylhydroxamic acid; D003575:Cytochromes c1; D005993:Glycerolphosphate Dehydrogenase; C036140:L-alpha-glycerol-phosphate oxidase; C005090:lawsone