Yang Danyin, Zhang Silu, Xu Qiongyao, Lu Shan, Xiao Guoxun, Zheng Lin, Zhao Mouming
School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, PR China.
School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, PR China; Shenzhen Porshealth Bioengineering Co., Ltd., Shenzhen, 518116, PR China.
Food Res Int. 2025 Oct;217:116847. doi: 10.1016/j.foodres.2025.116847. Epub 2025 Jun 10.
Our previous study has demonstrated that oral ingestion of collagen hydrolysates facilitated absorption of hydroxyproline (Hyp)-containing di- and tripeptides in the micromolar range. To elucidate how the peptides were generated and absorbed in vivo, simulated digestion supplemented with intestinal brush border membrane (BBM) enzymes and Caco-2 model were used to monitor their fates. Results showed that Xaa-Hyp dipeptides, Xaa-Hyp-Gly tripeptides, and Gly-Pro-Hyp were exclusively produced by BBM enzymes rather than gastroduodenal enzymes. Particularly, aminopeptidase N, carboxypeptidases, and dipeptidyl peptidase-IV played crucial roles. Production rates of Xaa-Hyp dipeptides and Xaa-Hyp-Gly tripeptides varied with contents of precursor peptides containing 3-4 residues present in CTH (low-molecular-weight collagen hydrolysate) and CH (high-molecular-weight collagen hydrolysate). Moreover, Hyp-containing di- and tripeptides could be transported intact across the cell monolayer, with the highest apparent permeability coefficient (P, (23.91 ± 3.18) × 10 cm/s) observed for Gly-Pro-Hyp. Molecular docking revealed a positive correlation between the P values and affinity to peptide transporter 1 of Xaa-Hyp dipeptides, providing a new insight from the perspective of interaction into permeability of the peptides resistant to hydrolysis by peptidase.
我们之前的研究表明，口服胶原蛋白水解物有助于吸收微摩尔范围内含羟脯氨酸（Hyp）的二肽和三肽。为了阐明这些肽在体内是如何产生和吸收的，我们使用了补充肠刷状缘膜（BBM）酶的模拟消化和Caco-2模型来监测它们的去向。结果表明，Xaa-Hyp二肽、Xaa-Hyp-Gly三肽和Gly-Pro-Hyp完全是由BBM酶而非胃十二指肠酶产生的。特别是，氨肽酶N、羧肽酶和二肽基肽酶-IV发挥了关键作用。Xaa-Hyp二肽和Xaa-Hyp-Gly三肽的产生率随CTH（低分子量胶原蛋白水解物）和CH（高分子量胶原蛋白水解物）中含3-4个残基的前体肽含量而变化。此外，含Hyp的二肽和三肽可以完整地穿过细胞单层，其中Gly-Pro-Hyp的表观渗透系数最高（P，(23.91 ± 3.18) × 10 cm/s）。分子对接显示P值与Xaa-Hyp二肽对肽转运体1的亲和力之间呈正相关，从相互作用的角度为抗肽酶水解的肽的渗透性提供了新的见解。
