Metabolism of alpha-alkoxy glyceryl monoethers in rat liver, in vivo and in vitro.
An investigation of the metabolism of(14)C and(3)H labeled alpha-isomers of C(16) and C(18) alkoxy monoethers, administered intravenously and added to liver slices, showed extensive cleavage of the ether bond in rat liver. Approximately 99% cleavage of the C(16ratio0) ether bond and approximately 94% cleavage of the C(18ratio0) ether bond occurred in rat liver within 6 hours after intravenous injection. With doubly labeled chimyl alcohol ((3)H and(14)C), acetylation and subsequent acetolysis demonstrated that less than 0.92% of the phosphatides and less than 1.52% of total lipid radioactivity were in the form of alkoxy ethers. Long-chain fatty alcohols and fatty acids were the principal products of the ether cleavage in the liver. The relative rate of(14)C incorporation from chimyl alcohol and batyl alcohol into triglycerides and phospholipids, respectively, demonstrates that the palmitic (from chimyl alcohol) and stearic (from batyl alcohol) acids formed after cleavage enter the free fatty acid pool. The liver contained most of the radioactive label in the lecithin and cephalin of the microsomal fraction. Incubation of the labeled batyl or chimyl alcohols with liver slices resulted in the same products as in the in vivo experiments. Less than 1.4% of the C(16) and C(18) alkoxy ethers was oxidized to(14)CO(2) during a 3-hour incubation. In view of the extensive cleavage of the ether bond by liver, the hemopoietic and radioprotective activities reported for the alkoxy ethers should be reevaluated in terms of their metabolic products.
Snyder
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Medical Division, Oak Ridge Institute of Nuclear Studies, Oak Ridge, Tennessee.
Pfleger
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