Inhibition of electron flow through complex I of the mitochondrial respiratory chain of Ehrlich ascites carcinoma cells by methylglyoxal.
The effect of methylglyoxal on the oxygen consumption of Ehrlich-ascites-carcinoma (EAC)-cell mitochondria was tested by using different respiratory substrates, electron donors at different segments of the mitochondrial respiratory chain and site-specific inhibitors to identify the specific respiratory complex which might be involved in the inhibitory effect of methylglyoxal on the oxygen consumption by these cells. The results indicate that methylglyoxal strongly inhibits ADP-stimulated alpha-oxo-glutarate and malate plus pyruvate-dependent respiration, whereas, at a much higher concentration, methylglyoxal fails to inhibit succinate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinol, an artificial electron donor. Moreover, methylglyoxal cannot inhibit oxygen consumption when the NNN'N'-tetramethyl-p-phenylenediamine by-pass is used. The inhibitory effect of methylglyoxal is identical on both ADP-stimulated and uncoupler-stimulated respiration. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of EAC-cell mitochondrial respiration by methylglyoxal. We suggest that methylglyoxal possibly inhibits the electron flow through complex I of the EAC-cell mitochondrial respiratory chain.
Ray
S
S
Department of Biochemistry, University College of Science, University of Calcutta, India.
Dutta
S
S
Halder
J
J
Ray
M
M
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology*; D004579:Electron Transport; D006873:Hydroquinones / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000494:pharmacology; D007700:Kinetics; D008314:Malonates / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D010101:Oxygen Consumption / Q000187:drug effects; D011765:Pyruvaldehyde / Q000494:pharmacology*
D000447:Aldehydes; D006873:Hydroquinones; D007656:Ketoglutaric Acids; D008314:Malonates; C014634:lactaldehyde; D011765:Pyruvaldehyde; C030290:malonic acid; D016660:NAD(P)H Dehydrogenase (Quinone); C016421:duroquinol