Fatty alcohol synthesis accompanied with chain elongation in liver peroxisomes

We have reported that the fatty alcohol destined to form the 1-alkenyl group of plasmalogen is synthesized as a nascent fatty alcohol within peroxisomes, from acetyl-CoA supplied by beta-oxidation. The present experiment was designed to confirm this peroxisomal fatty alcohol synthesis by using [1-14C]acetyl-CoA. Rats were fed for 2 weeks on chow containing 0.25% clofibrate, as a peroxisome proliferator. Peroxisomes were prepared from the rat liver to more than 85% purity, and incubated with [1-14C]acetyl-CoA in order to investigate suitable conditions for fatty alcohol biosynthesis. Dodecanoyl-CoA was the most suitable primer, and the reaction required NADH and/or NADPH as a reducing factor; NAD+ or NADP+ greatly inhibited the reaction, even if a significant amount of the reduced form still remained. The reaction proceeded linearly with respect to peroxisomal protein concentration and incubation time. Under the optimum conditions for fatty alcohol synthesis, 1 mg of peroxisomal protein could produce approx. 0.7 nmol of fatty alcohol per hour, and the main product was hexadecanol.