Energy dependence of lung phosphatidylcholine biosynthesis studied with CO hypoxia.
The energy dependence of lung phosphatidylcholine (PC) biosynthesis was evaluated by measuring incorporation of radiolabeled precursor substrates by the isolated perfused lung during carbon monoxide (CO)-induced hypoxia. Ventilation with gases containing 75 or 90% CO (plus 5% O2 and 5% CO2) resulted in a mean decrease of lung ATP content by 29 and 53%, respectively, and a significant decrease of [U-14C]glucose incorporation into free fatty acids and the fatty acyl moiety of lung PC. [9,10-3H]palmitate incorporation into lung PC was also decreased by hypoxia but [methyl-14C] choline incorporation was unaffected. For disaturated PC, incorporation of all three substrates was significantly depressed during CO ventilation. These results indicate that lung synthesis of PC is inhibited by alterations of lung energy state. The reactions in lung PC metabolism that are inhibited by this degree of energy limitation are the de novo synthesis of fatty acids from glucose, the acylation of exogenous palmitate, and the remodeling of PC into disaturated PC by the deacylation-reacylation pathway.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000502:physiology; D010168:Palmitates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D010168:Palmitates; D010713:Phosphatidylcholines; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate; D005947:Glucose; D002794:Choline; D010100:Oxygen