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Previous studies from this laboratory on the mechanism of O-alkyl bond formation using a microsomal system from Tetrahymena pyriformis have shown that O-alkyl lipid synthesized from dihydroxyacetone phosphate has exchanged one hydrogen stereospecifically from the 1-sn position of the glycerol moiety. Indirect evidence suggested that acyldihydroxyacetone phosphate, an intermediate in )-alkyl lipid synthesis, is probably not the locus of the exchange. In the present study in was shown that stable acyldihydroxyacetone phosphate incubated in the presence of tritiated water and Tetrahymena microsomes does not become tritiated. When hexadecanol is added to the system O-alkyl lipid is produced which has incorporated one atom of hydrogen for each mole of hexadecanol at all time periods examined. Experiments in Ehrlich ascites tumor cells have shown that the hydrogen exchange also occurs in a mammalian system. The results indicate that the mechanism of O-alkyl lipid ether bond formation involves a hydrogen exchange and that this exchange occurs after the formation of acyldihydroxyacetone phosphate.

O-Alkyldihydroxyacetone phosphate is synthesized enzymatically from hexadecanol and acyldihydroxyacetone phosphate. In this process there is a hydrogen exchange in which the pro-R hydrogen of C-1 of the sn-glycerol moiety is lost. This hydrogen is replaced by a hydrogen from the medium. In order to obtain additional information on the mechanism of ether bond formation, it would be of interest to know whether or not the hydrogen exchange results in a change of configuration in the product, O-alkyldihydroxyacetone phosphate. By using O-alkylglycerol prepared both chemically and enzymatically from isomerase-treated [1,3-3H2, 1,3-14C2] dihydroxyacetone phosphate and an O-alkylglycerol cleavage enzyme system, it was shown that the hydrogen exchange occurs with retention of configuration of the substituents of C-1 of the sn-glycerol moiety.