Metabolic fate of an antihyperuricemic peptide, Tyr-Leu-Asp-Asn-Tyr (YLDNY), upon ingestion in rats

Tyr-Leu-Asp-Asn-Tyr (YLDNY) is an orally active antihyperuricemic peptide. However, its metabolic fate after oral administration and mechanism of action remain unclear. YLDNY resisted pepsin digestion, and intact YLDNY, with smaller amounts of peptide fragments, remained in the stomach after administration to rats. In contrast, YLDNY was completely degraded by exopeptidase digestion and was not detected in the luminal contents of the anterior parts of the small intestine. Only a small quantity of tetrapeptide (Tyr-Leu-Asp-Asn (YLDN)) was detected in the luminal contents of the anterior parts of the small intestine, although there was no significant increase after administration. None of the intact or modified peptides increased in portal and abdominal bloods, stomach and liver extracts. However, hepatic xanthine levels increased significantly 2 h after YLDNY administration compared to amino acid mixture administration, suggesting hepatic xanthine oxidase activity suppression. This discrepancy implies the involvement of an alternative mechanism of stomach or gut-liver signaling.