Role of cardiolipin in the functioning of mitochondrial L-glycerol-3-phosphate dehydrogenase.
Adriamycin was used in situ, in isolated liver mitochondria of hyperthyroid rats to study the role of cardiolipin in the functioning of FAD-linked L-glycerol-3-phosphate dehydrogenase. The apparent kinetic parameters of the reaction catalyzed by the enzyme were affected by adriamycin. The effect of adriamycin was dependent on the electron acceptor, suggesting the existence of distinct binding sites for hydrophobic and hydrophilic acceptors. Assuming a correlation between the two plateaus observed upon binding of adriamycin to the mitochondria and the penetration of the drug into the two leaflets of the inner membrane [Cheneval et al. (1985) J. Biol. Chem. 260, 13003-13007], we can deduce that cardiolipin in both leaflets influences predominantly the electron acceptor binding site(s).
Beleznai
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Institute of Enzymology, Hungarian Academy of Sciences, Budapest.
Jancsik
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D000818:Animals; D001665:Binding Sites; D002308:Cardiolipins / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D005994:Glycerophosphates / Q000378:metabolism; D006980:Hyperthyroidism / Q000201:enzymology; D007700:Kinetics; D008297:Male; D008773:Methylphenazonium Methosulfate / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D014451:Ubiquinone / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism
D002308:Cardiolipins; D005994:Glycerophosphates; D014812:Vitamin K; D014451:Ubiquinone; D008773:Methylphenazonium Methosulfate; D004317:Doxorubicin; C029620:alpha-glycerophosphoric acid; D005993:Glycerolphosphate Dehydrogenase