Summary: | 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 (<i>p</i> < 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 (<i>p</i> < 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 (<i>p</i> < 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 <i>in vivo</i>. 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.
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