Producibility and digestibility of antihypertensive beta-casein tripeptides, Val-Pro-Pro and Ile-Pro-Pro, in the gastrointestinal tract: analyses using an in vitro model of mammalian gastrointestinal digestion.
Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are antihypertensive tripeptides isolated from milk fermented with Lactobacillus helveticus and inhibit angiotensin-converting enzyme (ACE). We investigated whether these peptides were generated from beta-casein by digestive enzymes and whether they were resistant to enzymatic hydrolysis, using an in vitro model. VPP and IPP were not generated from beta-casein by gastrointestinal enzymes; instead, a number of longer peptides including VPP and IPP sequences were detected. The fermentation step would therefore be necessary to produce these antihypertensive tripeptides. VPP and IPP themselves were hardly digested by digestive enzymes, suggesting that orally administered VPP and IPP remain intact in the intestine, retaining their activity until adsorption. The present study also demonstrated that various functional peptide sequences in beta-casein were resistant to gastrointestinal enzymes. There may be a strong correlation between the resistance of peptides to gastrointestinal digestion and their real physiological effects after oral administration.
Ohsawa
Kazuhito
K
Research and Development Center, Calpis Company, Ltd., 11-10, 5-chome, Fuchinobe, Sagamihara-shi Kanagawa 229-0006, Japan. kazuhito.oosawa@calpis.co.jp
Satsu
Hideo
H
Ohki
Kohji
K
Enjoh
Masashi
M
Takano
Toshiaki
T
Shimizu
Makoto
M
D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D018938:Caco-2 Cells; D002364:Caseins / Q000737:chemistry*; D004063:Digestion; D004355:Drug Stability; D005285:Fermentation; D041981:Gastrointestinal Tract / Q000201:enzymology*; D006801:Humans; D008892:Milk / Q000737:chemistry; D009842:Oligopeptides / Q000096:biosynthesis / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism
D000959:Antihypertensive Agents; D002364:Caseins; D009842:Oligopeptides; D010446:Peptide Fragments; C489032:isoleucyl-prolyl-proline; C489031:valyl-prolyl-proline