Whole body protein kinetics using Phe and Tyr tracers: An evaluation of the accuracy of approximated flux values

Phenylalanine (Phe) kinetics are increasingly used in studies of amino acid kinetics, because the metabolic fate of Phe is limited to incorporation into protein (protein synthesis, S(p)) and catabolism via hydroxylation (Q(pt)) to tyrosine (Tyr). Besides an infusion of labeled Phe to measure Phe flux (Q(p)), a priming dose of Tyr and an independent Tyr tracer are used to measure Tyr flux (Q(t)) and Q(pt). Alternatively, Q(t), Q(pt), and S(p) can be approximated by using equations, based on Phe and Tyr concentrations in body proteins, that eliminate the need for a Tyr tracer. To evaluate the accuracy of this approach, data were obtained from 12 type I diabetic patients and 24 nondiabetic control subjects who were studied with the full complement of tracers both with and without insulin infusion. S(p) approximations closely matched measured values in both groups (mean difference <2%, all values <5%), but the agreement was poor for Q(pt) (error range = -8 to +43%) and Q(t) (error range -22 to +41%). Insulin status had no effect on these comparisons. The lower approximation error for S(p) vs. Q(pt) is due to the small contribution (~10%) of Q(pt) to Q(p). Approximation error for Q(pt) (r > 0.99) can be explained by variability in the ratio of Tyr to Phe coming from protein breakdown, (Q(t) - Q(pt))/Q(p). Ideally, all fluxes should be directly measured, but these data suggest that whole body S(p) can be approximated with an acceptably small margin of error. However, the same equations do not yield reliably accurate values for Q(pt) or Q(t).