The choline incorporation pathway: primary mechanism for de novo lecithin synthesis in fetal primate lung

Abstract

The two pathways of de novo lecithin synthesis, choline incorporation (I) and phosphatidylethanolamine methylation (II), were examined in lung slices from rhesus monkey fetuses throughout the last half of gestation. Incorporation rates of pathway-specific radioactive precursors were used as a measure of lecithin production. At all stages of development studied, pathway I incorporated 10-50 times more precursor ([14C]choline) into lecithin than did pathway II ([14C]methionine or [14C]ethanolamine). In addition, although methylation activity did not change significantly during gestation, choline incorporation showed three distinct phases: (1) a stable, relatively low rate in early gestation, (2) an abrupt, twofold increase at approximately 90 percent of term, and (3) a return to lower activity levels in late gestation. This correlates with reports that lung lecithin concentration in fetal primates increases significantly in the last 10 percent of gestation. The lecithin to spingomyelin (L/S) ratios measured in amniotic fluid samples obtained at abdominal delivery were compared with pathway activities in lung slices from the same fetuses. Significant correlation was found between the amniotic fluid L/S ratio and pathway I activity (r = 0.77, P less than 0.001); in contrast, pathway II activity showed no relationship to the amniotic fluid L/S ratio. Thus, the L/S ratio appears to be a reflection of lung lecithin synthesis through the choline pathway. The conclusion that the choline pathway is the primary route of de novo lecithin synthesis in the nonhuman fetal primate lung is supported by three lines of evidence, (1) the predominance of choline incorporation into lecithin, (2) the late gestational rise in conversion of choline to lecithin, and (3) the correlation between pathway I activity and both lung lecithin concentration and amniotic fluid L/S ratio.