Metabolism of 2-hexadecynoate and inhibition of fatty acid elongation.
Dietary methyl-2-hexadecynoate appeared to inhibit fatty acid elongation in intact animals (Wood, R., Lee, T., and Gershon, H. (1980) Lipids 15, 141-150). Data from the present in vitro studies indicate that the microsomal elongation system is inhibited preferentially to the mitochondrial system. A series of metabolic acyl-CoA thioester intermediates has been isolated, characterized, and identified from microsomal and mitochondrial incubations with the 2-hexadecynoic acid (16 identical to 1 delta 2). The data support the following conclusions: 1) 16 identical to 1 delta 2 is activated to the CoA ester; 2) 16 identical to 1 delta 2 is acted on by an isomerase to produce a 2,3-allene; 3) either 16 identical to 1 delta 2 or the allene, or both, are hydrated to yield a beta-keto-CoA thioester after rearrangement; 4) the beta-keto ester is reduced to the beta-hydroxyacyl-CoA; 5) dehydration of the beta-hydroxy ester gives rise to trans-delta 2-hexadecenoate which accumulates; and 6) accumulation of the latter results from the inhibition of enoyl-CoA reductase by the 2,3-allene. The occurrence of cis and trans delta 3-hexadecenoates indicates the allene is reduced, after which the delta 3 monoene isomer may be isomerized to the delta 2 monoene by the acetylene isomerase or a different enzyme. Indirect evidence suggests that the fatty acid elongation systems may also be inhibited at another site.
D000480:Alkynes; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats
D000480:Alkynes; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; C031203:2-hexadecynoic acid