Abstract
Fatty acids are integral components of both pulmonary surfactant and cell membranes. De novo fatty acid synthesis in adult tissues is regulated by the interplay of nutrition and hormones on the content of rate limiting enzymes, their state of phosphorylation and the concentration of allosteric effectors. To determine if de novo fatty acid synthesis in developing lung is regulated by similar factors, we measured the activity of the rate limiting enzyme acetyl-CoA carboxylase and its in vitro regulatory characteristics in fetal, newborn and adult rat lung. In fetal lung, acetyl-CoA carboxylase activity, measured in 100,000xg cell supernatant, increased from 1.01 nmoles/min/mg protein at 19 days gestation to 3.15 nmoles/min/mg protein by term (22 days). By one day after birth, activity fell to 30% of the peak fetal value. Activity remained low at 1, 2 and 3 weeks of age and in adult lung. In vitro activity of enzyme from fetal lung was greatly influenced by allosteric effectors: 2.0 mM citrate increased activity 5 fold while 25μM palmitoyl-CoA decreased activity by 75%. Pre-incubation in dephosphorylating conditions (10mM Mg++) resulted in a 50% increase in activity while phosphorylating conditions (2mM Mg++ - 4mM ATP) decreased activity 86%. These data demonstrate that acetyl-CoA carboxylase is very active in fetal lung, and the activity falls to low levels in the newborn period. In addition, in vitro regulation of the enzyme in fetal lung was qualitatively similar to that reported for adult liver, suggesting that fetal lung enzyme activity is modulated by similar mechanisms.
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Maniscalco, W., Finkelstein, J. & Shapiro, D. 1689 REGULATION OF FATTY ACID SYNTHESIS IN DEVELOPING RAT. Pediatr Res 15 (Suppl 4), 725 (1981). https://doi.org/10.1203/00006450-198104001-01708
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DOI: https://doi.org/10.1203/00006450-198104001-01708