Metabolism of plasma-derived B-methyl-heptadecanoic acid in adult, awake rat brain

The authors have determined the utilization of [1-14C]-3-methyl-heptadecanoic acid (BHM), a beta-methyl fatty acid analog considered unable to undergo beta-oxidation, by brain in awake, 3 month-old Fischer-344 rats. BMH purity, structure, and mass were verified by TLC, NMR, and EI-MS. The distribution of radioactivity between CO2, water-soluble metabolites, lipids, and proteins was measured in plasma and brain after an intravenous bolus administration. Plasma radioactivity decreased rapidly within 20 min after injection, whereas the proportion of plasma 14CO2 increased to represent 20% of plasma radioactivity from 10-20 min, 6% at 1 h, and less thereafter. Total brain radioactivity peaked at 45 min, and decreased by 50% at 4 h and by 70% at 48 h. The proportion of label in the lipid fraction initially declined very rapidly, representing only 15% of total brain radioactivity at 1 h with 70 and 15% in the water-soluble and protein fractions. However, by 4 h, the lipid, protein, and aqueous compartments contained 30, 25, and 45% of the brain label, respectively, and 50, 35, and 15% at 48 h. Amino acids comprised most of the water-soluble radioactivity, with the combined glutamate and glutamine pools containing 60-70% of the aqueous label from 5 min to 6 h. Therefore, in addition to being incorporated into brain lipids, significant oxidation of BMH occurred, labelling brain amino acids and proteins, such that the decrease in brain radioactivity primarily represents decreasing water-soluble radioactivity