Cerebral Metabolism of Isotopic Glucose in Normal Human Subjects

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

Using a method previously described by the author, the total activity of labeled carbon dioxide in the blood entering and leaving the brain was determined following a single injection of C¹⁴-labeled glucose into normal human subjects. The variously labeled isotopes used as substrates were glucose-U-C¹⁴ (uniformly labeled glucose), glucose-1-C¹⁴, glucose-2-C¹⁴ and glucose-6-C¹⁴. An estimation of the fraction of the cumulative C¹⁴O₂ resulting from the oxidation of labeled glucose, over a 90-minute time interval following injection, showed that an average of 14.6% of the injected C¹⁴ was converted into C¹⁴O₂, by the brain, when glucose-U-C¹⁴ was the isotope injected. With glucose-1-C¹⁴ as the substrate, an average of 7.3% was found. When glucose-6-C¹⁴ was used, an average of 7.0% was found, and with glucose-2-C¹⁴ as the injected substrate, 10.8% of the injected C¹⁴ was converted into C¹⁴O₂. Theoretical considerations of the data, using some equations currently employed for estimating the role of the hexose monophosphate shunt in glucose metabolism, suggested that practically all of the glucose-derived CO₂ arose glycolytically. However, when ‘specific activities’ of the ‘added increment’ C¹⁴O₂ (i.e. the ‘specific activity’ of the CO₂ produced by the brain and added to the venous blood leaving the brain) were determined, the data seemed to warrant a serious consideration that there is a constant production, by the brain, of CO₂ from some source(s) other than glucose.