Tricarboxylic acid cycle activity in perfused rat lungs after O2 exposure.
O2-induced impairment of mitochondrial energy generation was examined in intact lungs isolated from rats after 18-30 h exposure to either air or 100% O2 in vivo. Mitochondrial metabolic rates were determined by separate measurements of 14CO2 production from [1-14C]pyruvate and [U-14C]palmitate, perfused under normal and stimulated metabolic conditions brought about by perfusion with the uncoupler of oxidative phosphorylation, 2,4-dinitrophenol (DNP). In the absence of DNP, O2 exposure did not significantly alter 14CO2 productions from either substrate. DNP increased lung pyruvate and palmitate catabolism to CO2 twofold in air-exposed lungs but did not alter 14CO2 production in lungs isolated from O2-exposed rats. These data demonstrated an O2-induced impairment of maximal mitochondrial metabolism of both pyruvate and palmitate that could not be explained by alterations in tissue free coenzyme A or by loss of pyridine nucleotides. However, comparisons of the steady-state levels of tricarboxylic acid cycle intermediates between O2- and air-exposed lungs did identify isocitrate dehydrogenase as a possible site of O2-induced enzyme inactivation.
Bassett
D J
DJ
Division of Physiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Reichenbaugh
S S
SS
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects*; D003065:Coenzyme A / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011652:Pulmonary Circulation; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D007656:Ketoglutaric Acids; D010169:Palmitic Acids; D011773:Pyruvates; D006153:Guanosine Diphosphate; D019308:Palmitic Acid; D006157:Guanosine Monophosphate; D019289:Pyruvic Acid; D006160:Guanosine Triphosphate; D010100:Oxygen; D003065:Coenzyme A