Cl4 STUDIES IN CARBOHYDRATE METABOLISM

After a single injection of uniformly labeled glucose-Cl4 into rats (1) and dogs (2), the specific activity of plasma glucose, highest immediately after the injection, declines exponentially. The decline is due to a progressive replacement of the tagged compound with relatively non-labeled glucose. The slope or rate constant of the decay curve denotes the rate of turnover of the glucose pool expressed as the fraction of its total glucose content replaced per unit of time. The curve of specific activity for expired COZ at first rises gradually, and then, after reaching a peak at approximately 1 hour, declines with a slope somewhat less than that of glucose. As pointed out by Stetten et al. (3), this curve is incompatible with the assumption of a one pool model which was made by earlier workers (1) who studied glucose oxidation rates. However, the contour of the CO2 curve is compatible with that of a glucose end-product incorporating Cl4 atoms which have traversed at least two sizable pools, each with a turnover time of appreciable magnitude. One of these pools is obviously glucose. Another one which is known to exist in the direct pathway of glucose degradation is the large reservoir of HCOI-COZ. If it is assumed that the two pools mentioned above are the only sizable ones in the pathway of early glucose degradation, the rates of glucose oxidation may be estimated. The mathematical treatment of the kinetics of enrichment and dilution of tracer material passing through a two pool series is well known. An exponential formula, long in use to describe radioactive transformations (4), has been applied both in metabolic problems (5-13) and in studies of blood flow in which dye dilution was employed (14). For application of the formula in the present study the rate constants of turnover for the glucose and HC03-CO2 pools must be known. That of glucose may be approximated, while that of HCO&JOZ may be either independently measured or calculated. It is important to note that the classic formula which describes the concentration of test material in the second pool is ordinarily applied on the assumption that enrichment and dilution of this pool are accomplished without entrance of diluting