Low feed intake at weaning reduces intestinal glutathione levels and promotes cysteine oxidation to taurine in pigs.

Weaning stress in pigs is associated with low feed intake and poor nutrient utilization. Cysteine is a sulfur amino acid with key roles in pig production, but how cysteine metabolism and requirements are affected by weaning stress should be better defined. The objective of this study was to determine the collective impact of weaning and feed restriction on tissue cysteine metabolism. Pigs were weaned at 21-d age without access to feed (W; 6.90†±†0.81 kg; n†=†9; reflecting acute nutritional stress) or were not weaned and remained with the sow (nonweaned [NW]; 6.81†±†0.65 kg; n†=†8). At euthanasia (23-d age), blood, bile, liver, jejunum, and ileum tissues were collected. Plasma, bile, and tissue amino acid and amino thiol concentrations were analyzed by HPLC. The activity of glutamate cysteine ligase (GCL) and glutathione synthetase (GSS), enzymes needed for glutathione (GSH) production, and cysteine dioxygenase 1 (CDO1) were determined with activity assays followed by HPLC analysis of reaction products. Plasma (271 vs. 192†±†19 µmol/L; P†<†0.001) and liver (417 vs. 298†±†33 nmol/g; P†<†0.05) Cys concentrations were increased in W compared to NW pigs. Despite greater plasma Cys, jejunum and ileum Cys content were not affected by weaning (P†>†0.10), whereas γ-glutamylcysteine (γ-GlyCys), the immediate precursor of GSH, declined in both jejunum (14.3 vs. 9.7†±†1.4 nmol/g; P†<†0.01) and ileum (11.2 vs. 6.4†±†0.8 nmol/g; P†<†0.001) in W pigs. Glutathione content was lower in the jejunum (1,379 vs. 1,720†±†70 nmol/g; P†<†0.05) and ileum (1,497 vs. 1,740†±†74 nmol/g; P†<†0.05) in W pigs. In the jejunum, GCL activity tended to be greater (0.56 vs. 0.39†±†0.07 nmol γ-GluCys • mg-1 • min-1; P†<†0.10), whereas GSS activity tended to be lower (1.11 vs. 1.38†±†0.10 nmol GSH • mg-1 • min-1; P†<†0.10) in W compared to NW pigs. In the ileum, the activities of GCL and GSS were not affected by weaning (P†>†0.10). Although liver CDO1 activity was not different between groups (P†<†0.10), liver taurine was greater in W compared to NW pigs (5,115 vs. 2,336†±†912 nmol/g; P†=†0.001). Bile concentrations of Cys (1,203 vs. 279†±†103 µmol/L; P†<†0.001) and cysteinylglycine (203 vs. 117†±†33 µmol/L; P†<†0.10), the direct product of GSH degradation, were greater in W compared to NW pigs. Collectively, these results suggest that systemic Cys is not effectively utilized for gut GSH production in newly weaned pigs; instead, it is oxidized to taurine and eliminated in bile.