Samuel J. Friedberg

Plasma transport forms of ingested fatty alcohols in the rat

Previous studies have shown that ingested fatty alcohols are absorbed as fatty acids and fatty acid esters, particularly triglycerides. The present study was carried out to determine whether fatty alcohols are also transported as 0-alkyl glyceryl ethers, alk-1-enyl glyceryl ethers, and as wax esters. Oxidation of fatty alcohols to other lipids was assessed by using a mixture of [1-3H] hexadecanol and [1-14C] hexadecanol of predetermined ratio. The results indicate that the absorption of fatty alcohol, and of its transport forms, parallels the absorption of labeled fatty acids. Six to 25% of plasma radioactivity was present as 1-0-alkyl diacylglyceryl ethers with a smaller proportion of ether lipids in the phospholipid fraction. In addition, 4–13% of the ingested hexadecanol appeared in the plasma as a material having the chromatographic properties of wax ester. Fatty alcohols were not detected in the plasma as alk-1-enyl lipids.

O-alkyl lipid synthesis: the mechanism of the acyl dihydroxyacetone phosphate fatty acid exchange reaction.

We have previously provided evidence for a mechanism by which acyl DHAP is converted enzymatically to O-alkyl DHAP. This mechanism involves, in part, the formation of an endiol of acyl DHAP, loss of the fatty acid by splitting of the DHAP carbon-1 to oxygen bond and the gain of a long chain fatty alcohol. It has been shown that acyl DHAP can exchange its fatty acid for one in the medium, presumably by the mediation of O-alkyl DHAP synthase. In the present investigation we have shown that the fatty acid which is gained by acyl DHAP in the exchange process retains both carboxyl oxygens, as predicted by our postulated mechanism. This reaction is exceptional because the usual action of acyl hydrolases is to cleave at the oxygen to acyl bond.

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.