Sizing up surfactant synthesis

Abstract

Phosphatidylcholine is generated through de novo synthesis and remodeling involving a lysophospholipid. In this issue of Cell Metabolism, research from the Shimizu lab (Harayama et al., 2014) demonstrates the highly selective enzymatic behavior of lysophospholipid acyltransferases. The authors present an enzymatic model for phosphatidylcholine molecular species diversification that impacts surfactant formation.

Figure 1. Pathways of Surfactant Generation

Top: The de novo pathway involves the acylation of lysophosphatidic acid catalyzed by a lysophosphatidic acid acyltransferase (LPAAT) generating phosphatidic acid. LPAAT exhibits substrate selectivity for linoleoly CoA or docosahexaenoly CoA (18:2 or 22:6, respectively) as acyl groups. Phosphatidic acid in a series of subsequent steps (not shown) can be converted to lysophosphatidylcholine, which lacks its sn-2 linked acyl group and in turn can serve as a substrate for the remodeling pathway. Bottom: In phosphatidylcholine (PC) remodeling in lung epithelia, lysophosphatidylcholine is reacylated with palmitoyl CoA through actions of a lysophosphatidylcholine acyltransferase (LPCAT) at the sn-2 position of the glycerol backbone. Unlike LPAATs, LPCATS exhibit substrate selectivity for palmitoyl CoA (or oleoyl-CoA, not shown). This reaction generates the product, dipalmitoyl phosphatidylcholine, the major surface-active component of surfactant.