Inhibition of mitochondrial fatty acid elongation by antibodies to 3-ketoacyl-CoA thiolase.

Antibodies to pig heart 3-ketoacyl-CoA thiolase inhibited almost completely and in a parallel fashion thiolase and the acetyl-CoA-dependent fatty acid elongation system present in an acetone powder extract of pig heart mitochondria. This finding leads to the conclusion that mitochondrial fatty acid elongation occurs by reversal of fatty acid oxidation. Several lines of evidence point to the thiolase-catalyzed condensation reaction as the rate-limiting step in the formation of elongated products. However, the accumulation of hydroxy acids suggests the enoyl-CoA reductase activity is limiting in the synthesis of saturated fatty acids.