The proposed research will study those aspects of fatty acid metabolism which control the production and utilization of fatty acid for disaturated phosphatidylcholine biosynthesis in the pulmonary type II cell. These aspects are: 1. The activity of fatty acid desaturation, chain elongation, and chain shortening enzymes. These enzymes regulated the composition of the pool of fatty acids available for phosphatidylcholine biosynthesis. 2. The activity and selectivity of the acyltransferase enzymes, including those which carry out the deacylation-reacylation of phosphatidycholine. These enzymes select fatty acids fo phosphatidycholine biosynthesis from the pool of available fatty acids. We will also develop a new method for quantitating the importance of the ceacylation-reacylation cycle in type Ii cells. It is based upon the cell uptake and utilization of phosphatidic acids with defined fatty acid compostions. Two monolayer culture systems of type Ii cells will be used: 1. Type Ii cells will be isolated from the organ culture of fetal rabbit lung tissue. In culture, these cells produce a pulmonary surfactant similar to normal sufactant, but which contains a reduced level of palmitic acid. Reduced levels of palmitic acid are observed in the surfactant of human infants with the respiratory distress syndrome, and in human infants amd animals with essential fattu acid deficiencies. 2. Type II cells will be isolated from adult rabbit lung. These cells will serve as a control that exhibits normal type II cell fattty acid metabolism.
|Longmuir, K J; Haynes, S (1991) Evidence that fatty acid chain length is a type II cell lipid-sorting signal. Am J Physiol 260:L44-51|
|Longmuir, K J; Malinick, L A (1989) Transfer of phosphatidic acid from liposomes to cells is collision dependent. Am J Physiol 256:C522-31|
|Longmuir, K J; Resele-Tiden, C; Rossi, M E (1988) Fatty acids of pulmonary surfactant phosphatidylcholine from fetal rabbit lung tissue in culture. Biosynthesis of n-10 monoenoic fatty acids. J Lipid Res 29:1065-77|
|Longmuir, K J; Rossi, M E (1988) Fatty acid chain-shortening activity in the pulmonary type II cell. Biochim Biophys Acta 961:144-7|
|Longmuir, K J; Haynes, S (1988) Purification of long-chain, saturated, free fatty acids. J Chromatogr 454:438-43|
|Longmuir, K J; Rossi, M E; Resele-Tiden, C (1987) Determination of monoenoic fatty acid double bond position by permanganate-periodate oxidation followed by high-performance liquid chromatography of carboxylic acid phenacyl esters. Anal Biochem 167:213-21|