Cerebral Metabolism of Isotopic Lipid and Protein Derivatives in Normal Human Subjects

¹ From the Research Department, Albert Einstein Medical Center, Southern Division, Philadelphia, Pennsylvania

Protein and lipid derivatives were employed as substrates for determining cerebral metabolism in humans in vivo. The isotopes used were dl-glutamate-1-C¹⁴, l-glutamate-U-C¹⁴ (uniformly labeled), dl-glutamate-2-C¹⁴, l-lysine-U-C¹⁴, octanoate-1-C¹⁴, l-aspartate-U-C¹⁴, dl-aspartate-4-C¹⁴, urea-C¹⁴, butyrate-1-C¹⁴, glycerol-1, (3)-C¹⁴, glycerol-U-C¹⁴ and glycerol-2-C¹⁴. Of these substrates, only labeled aspartate, butyrate and glycerol were oxidized to C¹⁴O₂ by brain in vivo. An estimation of the fraction of the cumulative C¹⁴O₂ resulting from the oxidation of l-aspartate-U-C¹⁴, over a 90-minute time interval following injection, showed that 1.7% of the injected C¹⁴ was converted into C¹⁴O₂ by the brain. With butyrate-1-C¹⁴ an average of 3.9% was found. When glycerol-1, (3)-C¹⁴ was used, an average of 4.4% was found; with glycerol-2-C¹⁴, 7.2%; and with glycerol-U-C¹⁴ as the injected substrate, 9.9% of the injected C¹⁴ was converted into C¹⁴O₂. However, much of the brain C¹⁴O₂ in the case of the glycerol-C¹⁴ experiments could have been due to the oxidation of glucose-C¹⁴ which was synthesized by the body from the injected glycerol-C¹⁴. With aspartate-U-C¹⁴ and butyrate-1-C¹⁴ as substrates the formed glucose-C¹⁴ was insignificant. Comparison of ‘specific activities’ of ‘added increment’ C¹⁴O₂ with brain venous blood substrate ‘specific activities’ indicated that about 9.8% of brain CO₂ was derived from butyrate and about 2.3% from glycerol. The results offer evidence for cerebral metabolism of breakdown products of lipids and proteins in vivo.