The de novo and remodeling pathways of dipalmitoylphosphatidylcholine synthesis in lung epithelial cells are physiologically linked.

Abstract

Lung surfactant is essential for life and contains a critical molecule, dipalmitoylphosphatidylcholine (DSPtCho). Deficiency of surfactant DSPtdCho leads to atelectasis, mechanical abnormalities, and cardiovascular impairment. DSPtdCho production occurs by a de novo pathway and a remodeling pathway. A new enzyme involved in the remodeling pathway has recently been characterized, termed Acyl‐CoA:lysophosphatidylcholine acyltransferase (LPCAT). Preliminary results indicate that overexpression of LPCAT in lung epithelia decreases de novo PC synthesis while having no significant effect on PtdCho mass, indicating tight homeostatic control of DSPtdCho metabolism. Overexpression of LPCAT inhibited activity of the enzyme catalyzing the final step in the de novo synthesis pathway, cholinephosphotransferase (CPT). LPCAT overexpression reduced immunoreactive levels of two variants that exhibit CPT function, CEPT and CPT, without altering mRNA transcript levels for the enzymes. Thus, LPCAT is a critical enzyme that controls surfactant production by downregulating CPT activity either at the level of protein stability or by mRNA translational efficiency. These results further suggest that the remodeling and de novo pathways are physiologically linked.