Acute depletion of plasma glutamine increases leucine oxidation in prednisone-treated humans

Background, aims & methods To determine whether depletion in plasma glutamine worsens the catabolic response to corticosteroids, seven healthy volunteers received oral prednisone for 6 days on two separate occasions, at least 2 weeks apart, and in random order. On the sixth day of each treatment course, they received 5 h intravenous infusions of l-[1-14C]-leucine and l-[1-13C]-glutamine in the postabsorptive state (1) under baseline conditions (prednisone only day) and (2) after 24 h of treatment with phenylbutyrate (prednisone+phenylbutyrate day), a glutamine chelating agent. Results Phenylbutyrate treatment was associated with (1) an ≈15% decline in plasma glutamine concentration (627±39 vs. 530±31 μmol l−1; P<0.05), (2) no change in leucine appearance rate, an index of protein breakdown (124±9 vs. 128±9 μmol kg−1 h−1; NS) nor in non-oxidative leucine disposal, an index of whole body protein synthesis (94±9 vs. 91±7 μmol kg−1 h−1; NS), and (3) a ≈25% rise in leucine oxidation (30±1 vs. 38±2 μmol kg−1 h−1, P<0.05), despite an ≈25% decline (P<0.05) in leucine concentration. Conclusions In a model of mild, stress-induced protein catabolism, depletion of plasma glutamine per se may worsen branched chain amino acid and protein wasting.