Calculation of metabolic fluxes with anatomically separated sources of tracer and tracee

Traditional calculations of metabolic fluxes using isotope dilution are based on the assumption that tracer and tracee enter the distribution space through effectively identical ports. If the tracer infusion site is not identical with the site of endogenous release of the tracee, the traditional equations for calculating rate of appearance (Ra) of a metabolite may give rise to appreciable errors due to the presence of gradients in specific activity. When tracer and tracee enter by means of anatomically disparate sites, such as may be encountered in the study of metabolite (e.g., lactate, alanine, and glycerol) or free fatty acid turnover, one must employ a modification of the traditional specific activity. This modified specific activity is obtained as the ratio of tracer concentration "near" (in the same compartment as) the source of tracee to the concentration of tracee near the source of tracer infusion. This concept is employed to derive equations for calculating metabolic turnover in both steady- and non-steady-state conditions when entry sites of tracer and tracee are dissimilar.