Enzyme activities related to fatty acid synthesis in developing mammalian lung.

Abstract

Extract: Fatty acids are important components of pulmonary surface-active lipids and lung membranes. We have investigated fatty acid synthesis in developing rabbit lung by measuring the rate of incorporation of (14C)acetyl or (14C)malonyl-CoA into pentane-extractable fatty acids. Because the lung can incorporate exogenously supplied as well as endogenously synthesized fatty acid into phospholipid, parallel studies of hepatic fatty acid synthesis were carried out.Fatty acids can be synthesized in fetal rabbit lung by the de novo pathway and to a lesser extent by chain elongation. The activity of enzymes related to de novo fatty acid synthesis is at adult levels by 23 days of fetal life and remains fairly constant thereafter. Enzymes associated with hepatic de novo fatty acid synthesis reach very ‘high levels of activity during fetal life but this decreases by 50% after birth, in association with the onset of suckling. Activity of the enzymes of de novo pulmonary synthesis appears to be unaffected by birth and onset of nutritional intake.Pulmonary and hepatic fatty acid elongation do not appear to be major routes of fatty acid synthesis in the fetal rabbit. Microsomal elongation activity is low in the fetus and on the first day of life, adult activity being fourfold greater. Pulmonary mitochondrial elongation becomes progressively more active during fetal life, but quantitatively appears less important than de novo synthesis.Gas-liquid chromatography of the fatty acids synthesized by fatty acid synthetase in the supernatant fraction of lung homogenates revealed that the main product was palmitic acid, a major component of dipalmityl lecithin which is an important surface-active lipid. The maior products of pulmonary mitochondrial and microsomal fatty acid elongation were stearic acid and 20− and 22-carbon unsaturated fatty acids.The early maturation of the enzymes of the de novo pathway ensures a source of fatty acid for lung membrane growth and for surfactant formation when the pathways for lecithin synthesis mature.Speculation: Inasmuch as the enzymes associated with de novo fatty acid synthesis are active before the pathway for lecithin synthesis matures, fatty acid synthesis is probably not the rate-limiting factor in surfactant production in the rabbit fetus. The role of other lecithin precursors such as choline remains to be investigated.Early dietary intake does not appear to influence pulmonary fatty acid synthesis, but may play an important role in overall pulmonary lipid metabolism and the regulation of lung surface activity.