Extended Data Fig. 2 |. Clearance of metabolite boluses is consistent with mass action kinetics.

(a) Mice were fasted from 9 AM to 5 PM (8 h fasting). At 5 PM, mice were injected with an intravenous bolus of the indicated [U-¹³C] metabolite at a low, medium, or high dose (as specified in the methods). Blood was taken 5, 15, 30, and 60 min after the injection, and the concentration of labeled metabolite in serum was measured by LC-MS. For experiments involving branched-chain amino acids, all three were given together, with only the indicated amino acid in labeled form. Labeled metabolite concentration was plotted against time post bolus. Lines are exponential decay curves fitted with mean value of each group. (b) Pseudo-first-order consumption rate constants from bolus and perturbative infusions. The slopes (α) calculated from the infusion experiments were plotted against the elimination constants (γ) calculated from the bolus experiments for each circulating metabolite. Line is linear regression fit.