Properties of a Lysophospholipase-Transacylase from Rat Lung: Its Possible Involvement in the Synthesis of Lung Surfactant
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In 1961 Klaus et al. (1) first suggested that 1,2 dipalmitoyl-phosphatidylcholine (DPPC) comprised the functional constituent of the pulmanary surfactant, which prevents the lung alveoli from collapsing at low distending pressures. Ever since this discovery, there has been much interest in the synthesis and secretion of phospholipids, especially of DPPC, in lung. There are two routes for the de novo synthesis of phosphatidylcholine in lung, i.e. the classical CDP-choline pathway and the sequential N-methylation of phosphatidylethanolamine. Current knowledge indicates the former pathway to be by far the most important one (see refs. 2 and 3 for a review). Evidence from both in vitro and in vivo experiments suggests that the CDP-choline pathway produces primarily unsaturated species of phosphatidylcholine (4–7). Two auxiliary mechanisms, both involving lysophosphatidylcholine (lyso PC), are thought to play an important role in the conversion of unsaturated species into fully saturated species, mainly DPPC, of phosphatidylcholine. Firstly, acylation of 1-acyl lyso PC (8) with palmitoyl-CoA would lead to the formation of mainly DPPC, since the 1-position of the phosphatidylcholine precursor for the endogenous 1-acyl lyso PC is esterified for about 80% with palmitate (9–11). Secondly, a transacylation mechanism involving two molecules of 1-acyl lyso PC (12) would yield by the same argument mainly DPPC. Which of the two pathways contributes most to the synthesis of DPPC in vivo is still a matter of considerable debate and arguments in favour of both pathways can be provided. The specificity of acylCoA: lyso PC acyltransferases in lung microsomes is such that the incorporation of palmitate into the 2-position of 1-acyl lyso PC is higher than observed for liver microsomes, but no preferential esterification is observed when compared with unsaturated fatty acids (4,13,14). However, surfactant synthesis is generally believed to occur in alveolar type II cells (for a recent review see ref. 3) and the specificity of the acyltransferases of these cells may be masked in microsomes derived from total lung homogenate. Indeed, evidence has been provided which might indicate that the preference for palmitate in the acylation of 1-acyl lyso PC is higher in cells presumably derived from alveolar type II cells (15,16).
KeywordsAlveolar Type Lung Microsome Saturated Species Acceptor Function Unsaturated Species
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