Novel hemoglobin-derived xanthine oxidase inhibitory peptides: Enzymatic preparation and inhibition mechanisms

[Display omitted] •Hemoglobin was successively hydrolyzed by bromelain and GsProS8 for XO inhibition.•IVYPW, YPWTQ and LITGLW were novel XO inhibitory peptides.•Tyrosine boosted XO inhibition via hydrogen-bond and Pi-Sigma interaction with XO.•The sum of Pi-related interactions positively impacted X...

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Bibliographic Details
Published in:Journal of functional foods 2023-03, Vol.102, p.105459, Article 105459
Main Authors: Zhang, Peng, Jiang, Zhengqiang, Lei, Jia, Yan, Qiaojuan, Chang, Chang
Format: Article
Language:English
Subjects:
allopurinol
bromelains
Enzymatic hydrolysis
Geobacillus stearothermophilus
glutamic acid
Hemoglobin
hydrogen bonding
hydrolysates
hyperuricemia
Inhibition type
Molecular docking
peptides
tryptophan
tyrosine
uric acid
xanthine oxidase
XO inhibitory peptides
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Summary:[Display omitted] •Hemoglobin was successively hydrolyzed by bromelain and GsProS8 for XO inhibition.•IVYPW, YPWTQ and LITGLW were novel XO inhibitory peptides.•Tyrosine boosted XO inhibition via hydrogen-bond and Pi-Sigma interaction with XO.•The sum of Pi-related interactions positively impacted XO inhibition of peptides. Xanthine oxidase (XO) activity is critical to modulate uric acid and hyperuricemia. Hemoglobin was hydrolyzed by bromelain and the protease from Geobacillus stearothermophilus (GsProS8) to express excellent protein recovery rate (54.87%) and XO inhibitory activity (IC50 of 0.744 mg/mL), resulting from higher contents of tryptophan, glutamic acid and glycine. The hydrolysate was fractionated and identified three novel XO inhibitory peptides IVYPW, YPWTQ, and LITGLW (IC50 of 0.63–1.09 mM). Unlike allopurinol, IVYPW and YPWTQ were mixed-type inhibitors, whereas LITGLW was a non-competitive inhibitor. In addition to the well-recognized contribution of tryptophan, molecular docking studies revealed tyrosine residue in IVYPW and YPWTQ importantly enhanced XO inhibitory activities via hydrogen-bond and Pi-Sigma interactions with Thr1010 and His875, respectively. The total number of Pi-related interactions positively determined XO inhibition as comparing IVYPW, YPWTQ and LITGLW. This study provided a promising strategy to prepare anti-hyperuricemic peptides and understand inhibition mechanisms for the management of hyperuricemia.
ISSN:1756-4646
2214-9414
DOI:10.1016/j.jff.2023.105459