The mechanism of ether bond formation in O-alkyl lipid synthesis in Ehrlich ascites tumor. Unusual cleavage of the fatty acid moiety of acyl dihydroxyacetone phosphate.
We have previously presented evidence for the formation of 1-O-alkyl dihydroxyacetone-P from acyl dihydroxyacetone-P via the initial formation of an intermediate 1-O-acyl endiol of acyl dihydroxyacetone-P. This reaction involves a stereospecific exchange of the pro-R hydrogen of the acyl dihydroxyacetone-P moiety without change in configuration. The fatty acid is replaced by a long chain fatty alcohol which retains the oxygen of the primary carbinol. In the absence of fatty alcohol, water substitutes and the product is dihydroxyacetone-P which has also exchanged the pro-R hydrogen with a hydrogen from the medium. An absolute requirement of the proposed mechanism is that the loss of the fatty acid must proceed via an unusual cleavage of the dihydroxyacetone-P C-1 to oxygen bond instead of the usual cleavage at the fatty acid acyl to oxygen bond. In the present investigation, we have synthesized hexadecanoyl dihydroxyacetone-P containing oxygen-18 exclusively at the dihydroxyacetone-P C-1 oxygen. Using this substrate, we have shown that cleavage of hexadecanoyl dihydroxyacetone-P at the C-1 to oxygen bond is linked to O-alkyl dihydroxyacetone-P synthesis. Inhibition of O-alkyl lipid synthesis by means of magnesium or NADPH inhibited the unusual cleavage. At the same time, we have shown that there was hydrolysis of acyl dihydroxyacetone-P which proceeded by the usual mechanism and which was not related to synthesis of O-alkyl dihydroxyacetone-P.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D004099:Dihydroxyacetone Phosphate / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D008055:Lipids / Q000096:biosynthesis*; D013058:Mass Spectrometry; D051379:Mice; D010103:Oxygen Isotopes; D014306:Trioses / Q000378:metabolism*
D007202:Indicators and Reagents; D008055:Lipids; D010103:Oxygen Isotopes; D014306:Trioses; C003037:palmitoyl dihydroxyacetone phosphate; D004099:Dihydroxyacetone Phosphate