title: Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal.
abstract: The effect of methylglyoxal on the oxygen consumption of mitochondria of both normal and leukaemic leucocytes was tested by using different respiratory substrates and complex specific artificial electron donors and inhibitors. The results indicate that methylglyoxal strongly inhibits mitochondrial respiration in leukaemic leucocytes, whereas, at a much higher concentration, methylglyoxal fails to inhibit mitochondrial respiration in normal leucocytes. Methylglyoxal strongly inhibits ADP-stimulated alpha-oxoglutarate and malate plus NAD+-dependent respiration, whereas, at a higher concentration, methylglyoxal fails to inhibit succinate and alpha-glycerophosphate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinone and cannot inhibit oxygen consumption when the N,N,N', N'-tetramethyl-p-phenylenediamine by-pass is used. NADH oxidation by sub-mitochondrial particles of leukaemic leucocytes is also inhibited by methylglyoxal. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of leukaemic leucocyte mitochondrial respiration by methylglyoxal. Methylglyoxal also inhibits l-lactic acid formation by intact leukaemic leucocytes and critically reduces the ATP level of these cells, whereas methylglyoxal has no effect on normal leucocytes. We conclude that methylglyoxal inhibits glycolysis and the electron flow through mitochondrial complex I of leukaemic leucocytes. This is strikingly similar to our previous studies on mitochondrial respiration, glycolysis and ATP levels in Ehrlich ascites carcinoma cells [Ray, Dutta, Halder and Ray (1994) Biochem. J. 303, 69-72; Halder, Ray and Ray (1993) Int. J. Cancer 54, 443-449], which strongly suggests that the inhibition of electron flow through complex I of the mitochondrial respiratory chain and inhibition of glycolysis by methylglyoxal may be common characteristics of all malignant cells.
authors.affiliation: Department of Biological Chemistry, Indian Association for the Cultivation of Science, Calcutta 700 032, India.
authors.forename: S
authors.initials: S
authors.lastname: Biswas
authors.forename: M
authors.initials: M
authors.lastname: Ray
authors.forename: S
authors.initials: S
authors.lastname: Misra
authors.forename: D P
authors.initials: DP
authors.lastname: Dutta
authors.forename: S
authors.initials: S
authors.lastname: Ray
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D002648:Child; D005260:Female; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism; D007938:Leukemia / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
chemical_list: D000447:Aldehydes; D007656:Ketoglutaric Acids; D013386:Succinates; D009243:NAD; C014634:lactaldehyde; D011765:Pyruvaldehyde; D000255:Adenosine Triphosphate; D019802:Succinic Acid