Fatty acid biosynthesis in developing fetal lung.

Abstract

Fatty acids are integral components of glycerolipids and hence of the phosphatidylcholine-rich pulmonary surfactant. There is ample evidence that the lung is able to synthesize fatty acids de novo. Toward the end of gestation as the fetus prepares for life outside the uterus, there is a surge in phosphatidylcholine synthesis. At the same time there is an increase in de novo fatty acid biosynthesis as well as in the activity of fatty acid synthase, the enzyme that catalyzes the final steps in fatty acid synthesis. Glucocorticoids have long been known to accelerate phosphatidylcholine biosynthesis in the fetal lung and they have also been found to stimulate fatty acid biosynthesis and fatty acid synthase activity. In fact, fatty acid synthase is the first, and so far the only, enzyme involved in lipid biosynthesis to be clearly identified as glucocorticoid inducible in fetal lung. De novo fatty acid biosynthesis may have two important roles relating to surfactant production during late fetal life. In addition to providing fatty acids for incorporation into surfactant phospholipids, recent data suggest that fatty acids may also directly regulate phosphatidylcholine biosynthesis by activation of choline-phosphate cytidylyltransferase, an enzyme catalyzing a rate-limiting step in its biosynthetic pathway.