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Angiotensin I-converting enzyme inhibitory peptides from the hydrolysis of Pacific hake fillets by commerical protease Cinq-Mars, Crystal Dawn


In addition to modifications of diet and lifestyle, angiotensin I-converting enzyme (ACE) inhibitory prescription drugs have been conventionally used to control high blood pressure. Recently, protein hydrolysates, mainly those from milk and fish sources, have been shown to exhibit ACE-inhibitory activity, the most potent of which are now being marketed as nutraceutical alternatives for treatment of hypertension. In this study, Pacific hake (Merluccius productus) fillet was investigated as a source of ACE-inhibitory peptides. Specifically, the objectives were to assess the effects of (1) hydrolysis conditions, (2) raw material variability, (3) ultrafiltration separation, (4) simulated gastrointestinal digestion, and (5) peptide-ACE preincubation on hydrolysate ACE-inhibitory activity in vitro to establish if further study of antihypertensive efficacy in vivo is warranted. Using Protamex® commercial protease according to a Response Surface Methodology (RSM) Central Composite Design, hydrolysis time and enzyme-to-substrate ratio factors were found to be the most significant predictors of ACE-inhibitory activity (P<0.001), with 125 minutes and 3.0%, respectively, producing hydrolysate with an IC₅₀ of 165 ± 9 μg peptides/mL; higher time-enzyme combinations showed no significant improvement in ACE-inhibitory activity (P>0.05). ACE-inhibitory activity of hydrolysates produced from fish of different catch months and Kudoa infections did not differ significantly (P>0.05). Ultrafiltration of hydrolysate to <1O kDa resulted in an IC₅₀value of 44 ± 7 μg peptides/mL, making it over 2.5 times more potent than the commercial product PeptACE® (IC₅₀ 114 ± 8 μg peptides/mL). However, after simulated gastrointestinal digestion, unfractionated hydrolysate and the <10 kDa fraction had similar activity at 1C₅₀ 90 ± 9 μg peptides/mL and 89 ± 4 μg peptides/mL, repectively, and PeptACE® was approximately 30% more active at IC₅₀ 64 ± 6 μg peptides/mL. Therefore, as a ’pro-drug type’ inhibitor released by gastrointestinal digestion, further enrichment processing of unfractionated Pacific hake hydrolysate is unnecessary. Further, the ACE-inhibitory activity of digested unfractionated and <10 kDa hydrolysates were not significantly affected by pre-incubation with ACE (P>0.05) and the latter was found to exhibit a competitive inhibitory mode. Together, these results suggest Pacific hake fillet hydrolysates are a commercially viable source of ACE-inhibitory peptides that necessitate further in vivo study.

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