title: Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk.
abstract: Angiotensin-converting enzyme (ACE) plays a central role in blood pressure regulation by producing the vasoconstrictor angiotensin II. The inhibition of ACE with natural inhibitors, as alternatives to avoid the side effect of synthetic drugs, is a major target in the prevention of hypertension. In this study, we examined the separated caseins and whey proteins of goat milk for the presence of ACE inhibitory peptides. Digestion of isolated whey proteins and caseins of goat milk by gastric pepsin generated soluble hydrolysates exhibiting significant inhibition of ACE compared to weak inhibition by undigested proteins. The hydrolysates were fractionated by size exclusion chromatography, Sephacryl S-100 column, into four fractions (F1-F4). The late-eluting fraction (F4) of either whey or caseins exhibited greater ACE inhibition. Peptides in both F4 fractions, isolated by RP-HPLC, exhibited variable ACE inhibitory activities with the hydrophobic peptide peaks being the most potent ACE inhibitors. MALDI-TOF MS/MS resulted in identification of three potent ACE inhibitory peptides: PEQSLACQCL from β-lactoglobulin (residues 113-122), QSLVYPFTGPI from β-casein (residues 56-66), and ARHPHPHLSFM from κ-casein (residues 96-106). The peptides from whey and caseins exert significant ACE inhibitory activities comparable to that of captopril, an antihypertensive drug, exhibiting IC50 values of 4.45 μM and 4.27 μM, respectively. The results introduce, for the first time, new potent ACE-inhibitory peptides that can be released by gastric pepsin of goat milk whey and caseins and thus may pave the way for their candidacy as anti-hypertensive bioactive peptides and prevention of associated disorders.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan.
authors.forename: Hisham R
authors.initials: HR
authors.lastname: Ibrahim
authors.affiliation: Department of Food Hygiene and Control, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
keywords: ACE, angiotensin I-converting enzyme; Angiotensin I-converting enzyme (ACE); Anti-hypertension; Bioactive peptides; Caseins; GCP, goat casein proteins; GWP, goat whey proteins; Goat milk; HA, hippuric acid; HHL, hippuryl-histidyl-leucine; HL, histidyl-leucine; MALDI-TOF/MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; P-GCP, pepsin digested-GCP; P-GWP, pepsin digested-GWP; TNBS, 2,4,6-trinitrobenzene sulfonate; TNP-, 2,4,6-trinitrophenyl; Whey