Acetylation of Phenylalanine Hydroxylase and Tryptophan 2,3-Dioxygenase Alters Hepatic Aromatic Amino Acid Metabolism in Weaned Piglets

Weaning significantly alters hepatic aromatic amino acid (AAA) metabolism and physiological functions. However, less is known about the regulating mechanism of hepatic AAA metabolism after weaning. A total of 200 21-day-old piglets (Duroc × Landrace) were assigned randomly to the control group and the weaning group. In this study, weaning significantly decreased the concentration of phenylalanine, tryptophan, and tyrosine in piglet livers (p < 0.05). Additionally, through the detection of liver AAA metabolites and metabolic enzyme activity, it was observed that hepatic tryptophan catabolism was enhanced, while that of phenylalanine was weakened (p < 0.05). Intriguingly, acetyl-proteome profiling of liver from weaned piglets showed that weaning exacerbated the acetylation of phenylalanine hydroxylase (PAH) and the deacetylation of tryptophan 2,3-dioxygenase (TDO). Analysis of PAH and TDO acetylation in Chang liver cells showed that acetylation decreased the PAH activity, while deacetylation increased the TDO activity (p < 0.05). Furthermore, metabolites of AAAs and the acetylation statuses of PAH and TDO in primary hepatocytes from weaned piglets were consistent with the results in vivo. These findings indicated that weaning altered the PAH and TDO activity by affecting the acetylation state of the enzyme in piglets’’ livers. Lysine acetylation may be a potential regulatory mechanism for AAA metabolism in response to weaning.