Opioid peptides milk proteins

Meisel, H. and FitzGerald, R. J. (2000). Opioid peptides encrypted in intact milk protein sequences. Br. J. Nutr. 84, S27-S31. 

Most of the known bioactive peptides derived from milk proteins are opioid peptides (Table V). Those derived from caseins are called casomorphins or casoxins, while those from whey proteins are lactorphins, lactoferroxins or serorphin. Major opioid peptides are fragments of (3-casein. 

Klebsiella pneumoniae infection in mice after intravenous treatment (Meisel and Schlimme, 1996). The mechanism by which milk protein derived peptides exert their immunomodulatory effects is not yet defined. However, opioid peptides may affect the immunoreactivity of lymphocytes via the opiate receptor. There is a remarkable relationship between the immune system and opioid peptides, because opioid p, receptors for endorphins are present on T lymphocytes and human phagocytic leukocytes (Meisel, 1998). 

Some of the peptides derived from milk proteins have more than one functional role, e.g., peptides from the sequence 60-70 of (3-cascin show immunostimulatory, opioid and ACE-inhibitory activities. This sequence has been defined as a strategic zone (Migliore-Samour and Jolles, 1988). The sequence is protected from proteolysis because of its high hydrophobicity and the presence of proline residues. 

Chiba, H. and Yoshikawa, M. 1986. Biologically functional peptides from food proteins new opioid peptides from milk proteins. In Protein Tailoring for Food and Medical Uses (R.E. Feeney and J.R. Whitaker, eds), pp. 123-153. Marcel Dekker, New York. 

Teschemacher, H., Koch, G., and Brantl, V. 1994. Milk protein derived atypical opioid peptides and related compounds with opioid antagonist activity (Review). In P-Casomorphins and Related Peptides Recent Developments (V. Brand and H. Teschemacher, eds), pp. 3-17. VCH, Weinheim. 

Yoshikawa, M., Tani, F., Yoshimura, T., and Chiba, H. 1986b. Opioid peptides from milk proteins. Agric. Biol. Chem. Tokyo 50, 2419-2421. 

In addition to the four classes of opioid peptides discussed earlier (Section3.4), other peptides of mammalian origin with opioid activity have also been identified. j3-Casomorphin (210), obtained by enzymatic digestion of the milk protein casein (659,660), exhibits some selectivity for jll receptors. Human j3-casomor-phin (211) differs from the bovine sequence in two positions the human /3-casomorphin pen-tapeptide and tetrapeptide fragments are less potent than the corresponding bovine peptides (661). Other peptides with affinity for opioid receptors include peptides derived from hemoglobin (see Ref 662). 

The functional properties of milk proteins in foods have recently been expertly treated by Holt and Roginski (2001). These authors described the antihypersensitive, opioid, immunomodulatory, and calcium-binding milk peptides, the antiviral properties of various milk components, and the antimicrobial activity of lactoperoxidase, lactoferrin, lactoferricins, casein peptides, and peptides from a-lactalbumin. 

Caseinomorphins. Several peptides with opioid activity have been isolated from enzymatic digests of milk proteins (see Fox and Flynn, 1992). Such peptides were first isolated from enzymatic digests of casein and characterized as a family of peptides containing 4-7 amino acids with a common N-terminal sequence, H.Tyr.Pro.Phe.Pro-, and 0-3 additional residues (Gly, Pro, He), i.e. residues 60-63/6 of -casein, and hence were called caseinomorphins (P-CM) 4 to 7, respectively. P-CM-5 is the most effective of these peptides, which are 300-4000 times less effective than morphine. P-CMs are very resistant to enzymes of the gastrointestinal tract (GIT) and appear in the contents of the small intestine following ingestion of milk. -CN f60-70 also has weak opiate activity but may be hydrolysed to smaller, more active P-CMs by peptidases in the brush border of the GIT. 

Thus, all the major milk proteins contain sequences which, when liberated by gastrointestinal proteinases, possess opioid activity. These peptides are very resistant to proteolysis by gastrointestinal proteinases and, because of their high hydrophobicity, can be absorbed intact from the intestine. They possess physiological activity in vitro but their activity in vivo is as yet uncertain. 

Lactorphins, milk protein-derived opioid peptides. 

Besides being important building blocks in the construction of proteins, some peptides possess their own biological activity. Milk, in particular, is a source of many biologically active peptides. The enzymatic hydrolysis of the milk protein casein releases opioid peptides, which have pharmacological activities such as analgesia and sleep-inducing effects. Other peptides derived from casein are involved in calcium flow in tissues and modification of the immune system response. Other milk peptides... 

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