Cyanide-resistant respiration in Taenia crassiceps metacestode (cysticerci) is explained by the H2O2-producing side-reaction of respiratory complex I with O2.
The nature of the cyanide-resistant respiration of Taenia crassiceps metacestode was studied. Mitochondrial respiration with NADH as substrate was partially inhibited by rotenone, cyanide and antimycin in decreasing order of effectiveness. In contrast, respiration with succinate or ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) was more sensitive to antimycin and cyanide. The saturation kinetics for O2 with NADH as substrate showed two components, which exhibited different oxygen affinities. The high-O2-affinity system (Km app=1.5 microM) was abolished by low cyanide concentration; it corresponded to cytochrome aa3. The low-O2-affinity system (Km app=120 microM) was resistant to cyanide. Similar O2 saturation kinetics, using succinate or ascorbate-TMPD as electron donor, showed only the high-O2-affinity cyanide-sensitive component. Horse cytochrome c increased 2-3 times the rate of electron flow across the cyanide-sensitive pathway and the contribution of the cyanide-resistant route became negligible. Mitochondrial NADH respiration produced significant amounts of H2O2 (at least 10% of the total O2 uptake). Bovine catalase and horse heart cytochrome c prevented the production and/or accumulation of H2O2. Production of H2O2 by endogenous respiration was detected in whole cysticerci using rhodamine as fluorescent sensor. Thus, the CN-resistant and low-O2-affinity respiration results mainly from a spurious reaction of the respiratory complex I with O2, producing H2O2. The meaning of this reaction in the microaerobic habitat of the parasite is discussed.
del Arenal
I Patricia
IP
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado postal 70-159, México 04510 D.F., México. darenal@bq.unam.mx
Rubio
M Esther
ME
Ramírez
Jorge
J
Rendón
Juan L
JL
Escamilla
J Edgardo
JE
D000818:Animals; D003486:Cyanides / Q000494:pharmacology*; D003552:Cysticercus / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013621:Taenia / Q000187:drug effects / Q000254:growth & development*
D003486:Cyanides; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I