ACE inhibitory peptides

In the field of food sciences, numerous ACE inhibitory peptides have been isolated from the digestion or enzymatic hydrolysis of natural... 

Table 1. Natural resources containing ACE inhibitory peptides and their BP lowering.

Vercruysse L, Smagghe G, Matsui T, Camp JV. (2008) Purification and identification of an angiotensin I-converting enzyme (ACE) inhibitory peptide from the gastrointestinal hydrolysate of the cotton leafworm, Spodoptera Littoralis. Process Biochem 43 900-904. 

Zhu XL, Watanabe K, Shiraishi K, Ueki T, Noda Y, Matsui T, Matsumoto K. (2008) Identification of ACE-inhibitory peptides in salt-free soy sauce that are transportable across caco-2 cell monolayers. Peptides 29 338-344. 

Mignel M, Aleixandre MA, Ramos M, Lopez-Fandino R. (2006) Effect of simnlated gastrointestinal digestion on the anti-hypertensive properties of ACE-inhibitory peptides derived from ovalbumin. J Agric Food Chem 54 726-731. 

TABLE 4.1 ACE-inhibitory peptides derived from shellfish origin, amino acid sequence, enzyme used for hydrolysis, and IC50 value... 

ACE-inhibitory peptides from invertebrates such as crustaceans have been reported. The sequential hydrolysis of defatted Antarctic krill muscle via pepsin and trypsin resulted in an ACE-inhibitory extract. The active peptide isolated from the extract was found to be Lys-Leu-Lys-Phe-Val, showing an IC50 value of 30jiM (Kawamura et ah, 1992). The other crustacean, Acetes chinensis, used the protease from Bacillus sp. 

FIGURE 4.3 Antihypertensive activities of ACE-inhibitory peptides after single oral administration in SHRs. SHRs were administered captopril (O), the ACE-inhibitory peptide from rotifer ( ) at a dose of 50mg/kg. Changes in systolic blood pressure were expressed as mean SE [n—5). Statistical analyses were done by Student t-test (P<0.05) (Skeggs et at., 1957). 

A. molpadioidea, was a novel ACE-inhibitory peptide, showing very low similarities to other ACE-inhibitory peptide sequences and was sequenced as Met-Glu-Gly-Ala-Gln-Glu-Ala-Gln-Gly-Asp (Zhao et al., 2009). 

Byun, H. G. and Kim, S. K. (2001). Purification and characterization of angiotensin I converting enzyme (ACE) inhibitory peptides from Alaska Pollack (Theragra chalcogramma) skin. Process Biochem. 36,1155-1162. 

Wang, J., Hu, J., Cui, Z., Bai, X., and Du, Y. (2008b). Purification and identification of a ACE inhibitory peptide from oyster proteins hydrolysate and the antihypertensive effect of hydrolysate in spontaneously hypertensive rats. Food Chem. Ill, 302-308. 

Zhao, Y., Dong, S., Liu, Z., Zhao, X., Wang, J., and Zeng, M. (2009). A novel ACE inhibitory peptide isolated from Acaudina molpadioidea hydrolysate. Peptides 30,1028-1033. 

Asn-Pro, Asp-Met, Asp-Leu, Ala-Val, and Gly-Val were isolated from fermented sardine sauce further, the ACE-inhibitory peptides Ala-Pro, Arg-Pro, Gly-Pro, and Ala-Gly-Pro were isolated from fermented bonito sauce. Val-Pro was also identified in salted and fermented anchovy by Lee (1996). Among the peptides identified by Ichimura et al. (2003), Ala-Pro, Lys-Pro, and Arg-Pro showed strong and similar inhibitory activity. Ichimura et al. (2003) also isolated nine types of peptides containing Pro residues in their carboxy terminals. Due to the unique structure of Pro as an imino acid, peptide bonds containing Pro residues are often resistant to hydrolysis by common peptidases. This may be the reason why these Pro-containing dipeptides survived after long-term fermentation. Among these peptides, Lys-Pro was further evaluated in vivo in male SHRs (Charles River Japan, Yokohama) by oral administration. As shown in Fig. 5.3, orally administered Lys-Pro shows a tendency to lower the blood pressure of SHRs. 

Fujita, H. and Yoshikawa, M. (1999). LKPNM A prodrug-type ACE-inhibitory peptide derived from fish protein. Immunopharmacology 44,123-127. 

Pihlanto-Leppala, A. (2001). Bioactive peptides derived from bovine proteins Opioid and ACE-inhibitory peptides. Trends Food Sci. Technol. 11,347-356. 

Tsai, J. S., Chen, J. L., and Pan, B. S. (2008). ACE-inhibitory peptides identified from the muscle protein hydrolysate of hard clam (Meretrix lusoria). Process Biochem. 43, 743-747. 

ACE inhibitory peptides have been separated from the skin of skate by Lee et ah (2011). The purified peptides showed IC50 values of 95 and 148 M, respectively, for both peptides isolated from the skin of skate. Further, Lineweaver-Burk plots indicated that the peptides act as noncompetitive inhibitor against ACE. Recently, many inhibitory peptides against ACE are reported (Table 15.2) as natural alternative biofunctional peptides that are safer than that of the existing artificial ACE inhibitory compounds in the market that show some side effects. Various peptides have been isolated from seafood by-products from the fisheries industry such as backbones from tuna (Lee et al., 2010). Tuna backbone has hydrolyzed using various proteases such as alcalase, a-chymotrypsin, neutrase, papain, pepsin, and trypsin to obtain an antioxidant peptide (Je et ah, 2007). 

Pripp, A. H., Isaksson, T., Stepaniak, L., and Sorhaug, T. (2004). Quantitative structure-activity relationship modeling of ACE-inhibitory peptides derived from milk proteins. 

Vercruysse, L., Van Camp, J., and Smagghie, G. (2005). ACE inhibitory peptides derived from enzymatic hydrolysates of animal muscle protein A review. ]. Agric. Food Chem. 53, 8106-8115. 

Marine fishes are rich sources of structurally diverse bioactive compounds including polyunsaturated fatty acids, polysaccharides, minerals, vitamins, antioxidants, enzymes, and bioactive peptides (Kim et ah, 2008). Marine fish-derived ACE inhibitory peptides have been purified from enzymatic digestion of various fish materials from Alaska pollack (Nakajima et ah, 2009), bonito (Fujita et ah, 2000 Hideaki et ah, 1993 Yokoyama et ah,... 

Nowadays, ACE inhibitory peptides have been isolated from meat, remaining muscle proteins, skin collagen and gelatin, bone, and internal organs of fishes such as Alaska pollack, bonito, tuna, salmon, shark, and sardine. Table 16.1 provides a partial summary of ACE inhibitory peptides derived from marine fish sources, their amino acid sequence, the enzyme used for hydrolysis, and IC50 values. The IC50 value is the concentration of peptide that inhibits 50% of ACE activity. 

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