ENZYMATIC PATHWAYS OF PHOSPHATIDYLCHOLINE (PC) BIO- SYNTHESIS IN DEVELOPING PRIMATE LUNG

Abstract

Respiratory distress syndrome has been associated with inadequate amounts of PC, the level of which increases in fetal lung during the last 10% of gestation. Enzymes exist for the synthesis of PC by two pathways: the “choline pathway” (I) and the “methylation pathway” (II). In studying the control of PC biosynthesis, we have discovered that lung from newborn and adult Rhesus monkeys contains only one enzyme for the first step of both pathways. This is a dual substrate specificity enzyme with choline kinase (CK) and ethanolamine kinase (EK) activity. The ratio of EK to CK is 0.3 in lung tissues from these sources.This ratio remains constant from the dialyzed, 40,000 xg supernatant fluid of lung homogenates to a 300-fold purified fraction. Furthermore, this ratio remains constant at 0.3 in lung tissue from Rhesus monkey fetuses of 111 to 159 days gestation. Other organs of newborn and adult Rhesus monkeys showed similar EK/CK ratios, except for liver, which had a ratio of 0.6. The higher ratio of EK to CK in liver was shown to be caused by the existence of an additional enzyme in this tissue, totally absent in lung, for the phosphorylation of ethanolamine. This liver enzyme was insensitive to inhibition by choline, while the lung EK activity was inhibited 50% by concentrations of choline as low as 0.005 mM. These findings lead us to conclude thst increased PC synthesis in fetal lung tissue cannot be caused by an increase of EK activity in pathway II. These data also provide further support for the predominance of pathway I in developing primate lung.