Studies on the effects of copper deficiency on rat liver mitochondria. II. Effects on oxidative phosphorylation.
Effects of dietary copper deficiency in rats on respiratory enzymes of isolated rat liver mitochondria have been studied. After 2 weeks of Cu-depletion, cytochrome c oxidase (EC 1.9.3.1) activity had declined by 42% and between 4 and 8 weeks exhibited between 20 and 25% of the activity of control mitochondria. Activities of NADH cytochrome c reductase (EC 1.6.99.3) and succinate cytochrome c reductase (EC 1.3.99.1), were unaffected initially but declined by 32 and 46%, respectively, after 8 weeks of Cu-depletion. After 4 weeks there was a significant (34%) decline in succinate supported state 3 respiration with only a modest (18%) decline in state 4 respiration. The ADP:O ratio was unaffected by Cu-depletion after 6 and 8 weeks of dietary Cu-restriction. State 3 respiration was significantly reduced after 6 weeks when glutamate/malate or beta-hydroxybutyrate were used as substrates, whereas state 4 respiration and ADP:O ratios were unaffected. The fall in state 3 respiration was of sufficient magnitude at 8 weeks to cause a significant decline in the respiratory control ratio with all substrates. Comparisons between the relative activities of cytochrome c oxidase and reductase activities in Cu-deficient preparations, the relatively specific effect of the deficiency on state 3 respiration with all substrates tested and the ability to increase significantly oxygen consumption in excess of maximal state 3 respiration by the uncoupler 2,4-dinitrophenol suggest that the defect in Cu-deficient mitochondria cannot be attributed solely to the decreased activity of cytochrome c oxidase.
Davies
N T
NT
Lawrence
C B
CB
Mills
C F
CF
D020155:3-Hydroxybutyric Acid; D000818:Animals; D003300:Copper / Q000172:deficiency*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006885:Hydroxybutyrates / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D051381:Rats; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D005971:Glutamates; D006885:Hydroxybutyrates; D008293:Malates; D013386:Succinates; D018698:Glutamic Acid; D003300:Copper; C030298:malic acid; D019802:Succinic Acid; D013384:Succinate Cytochrome c Oxidoreductase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D020155:3-Hydroxybutyric Acid