Structural specificity in ether lipid biosynthesis. Formation of hydroxyalkyl and oxoalkyl glycerophosphatides

Structural specificity of alkyl glycerolipid formation was studied in myelinating rat brain. 1,2-[2-14-C,2-3-H]Heptadecanediol, 1,2-[1-14-C]octadecanediol, and 1-O-2-hydroxy-[1-14-C]heptadecyl-rac-glycerol were administered intracerebrally and their incorporation into phospholipids was determined after time periods ranging from 6 to 48 hours. Experimental evidence is presented to support the following conclusions. (a) Long chain 1,2-alkanediols serve as direct precursors of the 2-hydroxyalkyl moieties of both choline and ethanolamine glycerophosphatides. (b) 1,2-Alkanediols are oxidized to 1-hydroxy-2alkanones which serve as precursors of the 2-oxoalkyl moieties of the glycerophosphatides. (c) Oxidations of hydroxy groups and reductions of oxo groups do not occur at the phospholipids, but are confined to 1,2-alkanediols and 1-hydroxy-2-alkanones, respectively. (d) Metabolic degradation of 1,2-alkanediols proceeds by oxidation to the corresponding 2-hydroxy and/or 2-oxo fatty acids and decarboxylation.