Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans

Abstract

The threonine dehydrogenase (TDG) pathway is a significant route of threonine degradation, yielding glycine in experimental animals, but has not been accurately quantitated in humans. Therefore, the effect of a large excess of dietary threonine, given either as free amino acid (+Thr) or as a constituent of protein (+P-Thr), on threonine catabolism to CO2 and to glycine was studied in six healthy adult males using a 4-h constant infusion ofl-[1-13C]threonine and [15N]glycine. Gas chromatography-combustion isotope ratio mass spectrometry was used to determine [13C]glycine produced from labeled threonine. Threonine intakes were higher on +Thr and +P-Thr diets compared with control (126, 126, and 50 μmol ⋅ kg−1 ⋅ h−1, SD 8, P < 0.0001). Threonine oxidation to CO2increased threefold in subjects on +Thr and +P-Thr vs. control (49, 45, and 15 μmol ⋅ kg−1 ⋅ h−1, SD 6, P < 0.0001). Threonine conversion to glycine tended to be higher on +Thr and +P-Thr vs. control (3.5, 3.4, and 1.6 μmol ⋅ kg−1 ⋅ h−1, SD 1.3, P = 0.06). The TDG pathway accounted for only 7–11% of total threonine catabolism and therefore is a minor pathway in the human adult.