caa a22 4500 469078626 CHVBK 20180323132942.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF00169009 doi (NATIONALLICENCE)springer-10.1007/BF00169009 Inhibition of aconitase by alloxan and the differential modes of protection of glucose, 3-O-methylglucose, and mannoheptulose [Elektronische Daten] [Sigurd Lenzen, Maritta Mirzaie-Petri] Summary: Alloxan inhibited aconitase with a half maximal inhibitory concentration of 0.5 mM in sonically disrupted and 2.3 mM in intact isolated liver mitochondria. For dialuric acid the half maximal inhibitory concentrations were 1.1 mM and 2.5 mM, respectively. Ninhydrin and N-ethylmaleimide (NEM) also inhibited aconitase with half maximal inhibitory concentrations in the submillimolar range and t-butylhydroperoxide (BuOOH) in the millimolar range, which, however, were not different for disrupted and intact mitochondria. Only the aconitase substrate citrate, but not glucose provided protection of the enzyme against inhibition. In intact liver cells the half maximal inhibitory concentration for alloxan was 6.8 mM. Again, dialuric acid and BuOOH were less potent inhibitors while ninhydrin and NEM were more potent inhibitors of aconitase in intact liver cells. In intact liver cells, glucose and 3-O-methylglucose, but not mannoheptulose and citrate provided protection against alloxan inhibition. The results show that aconitase is not an enzyme particularly sensitive towards alloxan inhibition and thus apparently not a primary site for mediation of alloxan toxicity as it is the glucokinase. This makes a primary site of alloxan action in the mitochondria extremely unlikely. On the other hand the results demonstrate that both the intact mitochondrial and plasma membrane as uptake barriers provide protection against alloxan toxicity. In addition the results clearly show, that 3-O-methylglucose provides protection against alloxan action only at the level of the plasma membrane through inhibition of alloxan uptake into the cell, while the site of protection of mannoheptulose is only the sugar binding site of the glucokinase. In contrast, glucose is shown here to be the only sugar with a dual protective effect both through inhibition of alloxan uptake through the plasma membrane like 3-0methylglucose and through protection of the glucokinase sugar binding site against alloxan inhibition of the en zyme like mannoheptulose. In the light of these results the unique protective potency of glucose as compared to that of other sugars is not surprising. Springer-Verlag, 1992 Aconitase nationallicence Alloxan nationallicence Ninhydrin nationallicence Glucose nationallicence Protection nationallicence Lenzen Sigurd Institute of Pharmacology and Toxicology, University of Göttingen, W-3400, Göttingen, Federal Republic of Germany aut Mirzaie-Petri Maritta Institute of Pharmacology and Toxicology, University of Göttingen, W-3400, Göttingen, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/5(1992-11-01), 532-536 0028-1298 346:5<532 1992 346 210 https://doi.org/10.1007/BF00169009 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00169009 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lenzen Sigurd Institute of Pharmacology and Toxicology, University of Göttingen, W-3400, Göttingen, Federal Republic of Germany aut NATIONALLICENCE 700 1- Mirzaie-Petri Maritta Institute of Pharmacology and Toxicology, University of Göttingen, W-3400, Göttingen, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/5(1992-11-01), 532-536 0028-1298 346:5<532 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer