Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome.
Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis.
Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome. Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis.