Phosphatidylcholine synthesis and pulmonary oxygen toxicity.
Oxygen at hyperbaric pressure causes a reduction of lung surfactant and inhibits the synthesis of phosphatidylcholine, the principal component of lung surfactant. Rabbit lung slices and broken cell preparations were used to determine whether phosphatidylcholine synthesis in general is inhibited or whether there is selective inhibition of surfactant dipalmitoyl-glycerophosphocholine synthesis. The incorporations of palmitate, oleate and choline into the phosphatidylcholine of lung slices are reduced to 44, 49 and 45% of the normal, respectively, in animals exposed to 100% oxygen at 3 atm. absolute for 4 h. The similarity of the level of phosphatidylcholine synthesis from these three precursors, as well as of the degree of inhibition, suggests a non-specific mechanism of inhibition of whole cell phosphatidylcholine synthesis. Broken cell preparations of lung incorporate palmitate and oleate into lysophosphatidylcholine at comparable rates when optimal amounts of precursors are used. This system is reduced to 60 and 73% of the normal for palmitate incorporation in homogenates and microsomal fraction, respectively and to 75 and 82% of the normal for oleate incorporation. Although the greater inhibition of palmitate incorporation over that of oleate is not statistically significant, an inhibition of the deacylation-reacylation mechanisms leading to palmitate incorporation may still be implicated as a factor in the toxicity of oxygen for surfactant phosphatidylcholine synthesis in view of the fact that with whole lung preparations, only one-tenth of the pulmonary cell population constitutes the surfactant producing type II alveolar cells (granular pneumocytes).
D000818:Animals; D002794:Choline / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D009829:Oleic Acids / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D010169:Palmitic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D011817:Rabbits
D009829:Oleic Acids; D010169:Palmitic Acids; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D003566:Cytidine Diphosphate Choline; D002794:Choline; D010100:Oxygen