The rate of formation of surface membrane ether lipids in Ehrlich ascites tumor cells: kinetic considerations

A previous investigation has shown that O-alkyl phospholipids are present in the surface membrane of Ehrlich ascites tumor cells. In the present investigation it was shown that 90% or more of [1-3H]hexadecanol injected intraperitoneally into mice bearing Ehrlich ascites tumors is taken up by the neoplastic cells in less than 15 min. Near maximum formation of surface membrane O-alkyl phospholipids requires approximately 8 h. The rate of accumulation of O-alkyl phospholipids is very similar both for the whole cell and for the surface membrane. Further examination of the data revealed that the conversion of hexadecanol into O-alkyl glycerophospholipids can be described by a simple model in which O-alkyl lipids appear at a single rate constant of 0.25 to 0.35 per hour and disappear at a rate of 0.02 per hour or less. These rate constants were obtained initially by stochastic analysis and validated both by deterministic methods and by compartmental analysis using the SAAM computer program. The method of kinetic analysis described may find broader application in providing comparative rate constants for the in vivo turnover of O-alkyl lipids in both normal and neoplastic tissues. The advantage of a stochastic approach is that kinetic data may be obtained with fewer assumptions relating to pool structure or specific models.