Presence of Modified\nPeptides with High Bioavailability\nand Angiotensin-Converting Enzyme Inhibitory Activity in Japanese\nFermented Soybean Paste (<i>Miso</i>)

Not only free amino acids and normal short-chain peptides\nbut also\nmodified amino acids, such as <i>N</i>-acetyl- and <i>N</i>-formyl amino acids, monoamines, polyamines, and modified\npeptides, such as isomerized aspartyl peptides, pyroglutamyl peptides,\nand diketopiperazines, were identified in Japanese fermented soy paste\n(<i>miso</i>) prepared using different fungal starters,\nrice, barley, and soybean-<i>koji.</i> One hour after oral\nadministration of water extract of soybean-<i>koji miso</i> to rats, the modified peptides increased significantly in the lumen\nupon the ingestion, while the normal peptides did not. In the blood\nfrom the portal vein and abdominal vena cava, 17 and 15 diketopiperazines,\n16 and 12 isomerized aspartyl peptides, and 2 and 1 pyroglutamyl peptides\nsignificantly increased to approximately 10–400 nM, respectively.\nThe modified peptides, which increased in rat blood, showed angiotensin-converting\nenzyme (ACE) inhibitory activity in a dose-dependent manner, indicating\nmultiple ACE inhibitory peptides with high bioavailability in <i>miso.</i> Among them, l-β-Asp-Pro showed the\nhighest ACE inhibitory activity (IC<sub>50</sub> 4.8 μM)