Transfer of carbon atoms from mevalonate to n-fatty acids.

The distribution of 14C in the unsaponifiable (neutral) and saponifiable (acidic) components of tissue lipids was examined 4, 24, and 72 hours after the subcutaneous injection of [2-14C]mevalonate into g-day-old rats. Of the total radioactivity contained in the unsaponifiable plus saponifiable material, 7 to 33% was in the acidic fraction obtained from the brain, spinal cord, and the skin, most of it (90% in the brain and spinal cord) being associated with palmitate and stearate in the ratio of 8:2 or 7:3,4 hours after the injections. Seventy-two hours after the injections the stearate became slightly more heavily labeled than palmitate in these three organs. The palmitate and stearate from the kidney and lung lipids became labeled also, but not as extensively as in the three organs of ectodermal origin. In contrast the n-fatty acids from liver did not contain detectable isotopic label. The incorporation of label into the two fatty acids in the brain and skin increased linearly with increasing doses of mevalonate. It is postulated that label from [2-W]mevalonate is diverted through a shunt to 3-hydroxy-3-methylglutaryl-CoA and free acetoacetate which is utilized preferentially for fatty acid synthesis in the brain, spinal cord, and the skin. Mechanisms which could account for the recycling of carbon atoms from intermediates of sterol biosynthesis are presented.