The aim of the present study was to perform an in silico evaluation of bovine meat proteins as potential precursors of biologically active peptides, as well as to determine whether such peptides can be released by selected proteolytic enzymes. The sequences of 19 bovine meat proteins were processed using the BIOPEP database and program. The profiles of potential biological activity of protein fragments were determined and the following parameters were calculated: the frequency of occurrence of fragments with given activity (A), the frequency of release of fragments with given activity by selected enzymes (AE), and the relative frequency of release of fragments with given activity by selected enzymes (W). Among the examined proteins, collagen and elastin appear to be the richest potential source of bioactive peptides, in particular of angiotensin-converting enzyme inhibitors, antithrombotic fragments, inhibitors of dipeptidyl peptidase IV and peptides regulating gastric mucosal activity. The high number of bioactive fragments in collagen and elastin is associated with a high content of glycine and proline, amino acids that are most abundant in biologically active fragments. Of the two investigated proteolytic enzymes, Proteinase K — an enzyme with broad specificity (e.g., against peptide bonds formed by the carboxyl groups of proline) can release considerably more biologically active fragments than Proteinase P1 — an enzyme with narrow specificity, not including proline residues.
Ansorge S., Bank U., Heimburg A., Helmuth M., Koch G., Tadje J., Lendeckel U., Woke C., Neubert K., Faust J., Fuchs P., Reinhold D., Thielitz A. and Täger M. ( 2009). Recent insights into the role of dipeptidyl aminopeptidase IV (DPIV) and aminopeptidase N (APN) families in immune function. Clinical Chemistry and Laboratory Medicine47: 253-261.
2.
Arai S. and Fujimaki M. ( 1991). Enzymatic modification of proteins with special reference to improving their functional properties. In: Fox P.F. (ed.), Food Enzymology, Vol. 2. London, New York: Elsevier, pp. 83-104.
3.
Arihara K. ( 2006). Strategies for designing novel functional meat products . Meat Science74: 219-229.
4.
Ashmarin I.P., Karazeeva E.P., Lyapina L.A. and Samonina G.E. ( 1998). The simplest proline-containing peptides PG, GP, PGP and GPGG: regulatory activity and possible source of biosynthesis. Biochemistry-Moscow63: 119-124.
5.
Byun H.G. and Kim S.K. ( 2002). Structure and activity of angiotensin I-converting enzyme inhibitory peptides derived from Alaskan pollack skin. Journal of Biochemistry and Molecular Biology35: 239-243.
6.
Caplice E. and Fitzgerald G.F. ( 1999). Food fermentations: Role of microorganisms in food production and preservation. International Journal of Food Microbiology50: 131-149.
7.
Chang A., Scheer M., Grote A., Schomburg I. and Schomburg D.(2009). BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009. Nucleic Acids Research37: D588-D592.
8.
Cheung H.S., Wang F.L., Ondetti M.A., Sabo E.F. and Cushman D.W. ( 1980). Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. Journal of Biological Chemistry255: 401-407.
9.
Cheung I.W.Y., Nakayama S., Hsu M.N.K., Samaranayaka A.G.P. and Li-Chan E.C.Y. ( 2009). Angiotensin-I converting enzyme inhibitory activity of hydrolysates from oat (Avena sativa) proteins by in silico and in vitro analysesJournal of Agricultural and Food Chemistry57: 9234-9242.
10.
Chrzanowska J. and Wojtatowicz M. ( 1999). Enzymy proteolityczne szczepionek serowarskich . Biotechnologia2(45): 131-144.
11.
Clar J.P. ( 2004). Fermentation - new products from an old process . Food Technology58(10): 75-76, 82.
12.
Dziuba M. and Darewicz M. ( 2007). Food proteins as precursors of bioactive peptides - division into families. Food Science and Technology International13: 393-404.
13.
Dziuba J. and Iwaniak A. ( 2006). Database of protein and bioactive peptide sequences . In: Mine Y. and Shahidi F. (eds), Nutraceutical Proteins and Peptides in Health and Disease, London: CRC - Taylor and Francis Group, pp. 543-563.
14.
Dziuba J., Iwaniak A. and Minkiewicz P. ( 2003). Computer-aided characteristics of proteins as potential precursors of bioactive peptides. Polimery48: 50-53.
15.
Dziuba J., Minkiewicz P., Nałecz D. and Iwaniak A. ( 1999). Database of biologically active peptide sequences . Nahrung43: 190-195.
16.
Dziuba J., Niklewicz M., Iwaniak A., Darewicz M. and Minkiewicz P. ( 2005). Structural properties of proteolytic-accessible fragments of selected animal proteins. Polimery50: 424-428.
17.
Friedman M. ( 1996). Nutritional value of proteins from different food sources. A review. Journal of Agricultural and Food Chemistry44: 6-29.
18.
Fyhrquist F. and Saijonmaa O. ( 2008). Renin-angiotensin system revisited. Journal of Internal Medicine264: 224-236.
19.
Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D. and Bairoch A. ( 2005). Protein identification and analysis tools on the ExPASy server. In: Walker J.M. (ed.), The Proteomics Protocols Handbook. Totowa, NJ, USA: Humana Press Inc., pp. 571-607.
20.
Hong F., Ming L., Yi S., Zhanxia L., Yongquan W. and Chi L. ( 2008). The antihypertensive effect of peptides: a novel alternative to drugs? Peptides29: 1062-1071.
21.
Iwaniak A. and Dziuba J. ( 2009). Analysis of domains in selected plant and animal food proteins - precursors of biologically active peptides. Food Science and Technology International15: 179-191.
22.
Jain E., Bairoch A., Duvaud S., Phan I., Redaschi N., Suzek B.E., Martin M.J., McGarvey P. and Gasteiger E. ( 2009). Infrastructure for the life sciences: design and implementation of the UniProt website. BMC Bioinformatics10: 136.
23.
Juillerat-Jeanneret L. and Gerber-Lemaire S. ( 2009). The prolylaminodipeptidases and their inhibitors as therapeutic targets for fibrogenic disorders. Mini-Reviews in Medicinal Chemistry9: 215-226.
24.
Kim S.K., Byun H.G., Park P.J. and Shahidi F. ( 2001). Angiotensin I converting enzyme inhibitory peptides purified from bovine skin gelatin hydrolysate. Journal of Agricultural and Food Chemistry49: 2992-2997.
25.
Kyte J. and Doolittle R.F. ( 1982). A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology157: 105-132.
26.
Leinonen R., Diez F.G., Binns D., Fleischmann W., Lopez R. and Apweiler R. ( 2004). UniProt archive. Bioinformatics20: 3236-3237.
27.
Lippi G., Favaloro E.J., Franchini M. and Guidi G.C. (2009). Milestones and perspectives in coagulation and hemostasis. Seminars in Thrombosis and Hemostasis35: 9-22.
28.
Mannucci E. and Rotella C.M. ( 2008). Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk. Nutrition, Metabolism and Cardiovascular Diseases18: 639-645.
29.
Maruyama S., Miyoshi S., Nomura G., Suzuki M., Tanaka H. and Maeda H. ( 1993a). Specifity for various imino-acid-residues of a proline-specific dipeptidylcarboxypeptidase from a Streptomyces species. Biochimica et Biophysica Acta, Protein Structure and Molecular Enzymology1162: 72-76.
30.
Maruyama S., Nonaka I. and Tanaka H. ( 1993b). Inhibitory effects of enzymatic hydrolysates of collagen and collagen-related synthetic peptides on fibrinogen/thrombin clotting. Biochimica et Biophysica Acta, Protein Structure and Molecular Enzymology1164: 215-218.
31.
McDonald A.G., Boyce S., Moss G.P., Dixon H.B. and Tipton K.F. ( 2007). ExplorEnz: A MySQL database of the IUBMB enzyme nomenclature . BMC Biochemistry8: 14.
32.
McDonald A.G., Boyce S. and Tipton K.F. ( 2009). ExplorEnz: The primary source of the IUBMB enzyme list . Nucleic Acids Research37: D593-D597.
33.
Meisel H. ( 2004). Multifunctional peptides encrypted in milk proteins . BioFactors21: 73-78.
34.
Meisel H., Walsh D.J., Murray B. and FitzGerald R.J. ( 2006). ACE inhibitory peptides. In: Mine Y. and Shahidi F. (eds), Nutraceutical Proteins and Peptides in Health and Disease, London: CRC - Taylor and Francis Group, pp. 269-315.
35.
Minkiewicz P., Dziuba J., Darewicz M., Iwaniak A., Dziuba M. and Nałecz D. ( 2008a). Food peptidomics. Food Technology and Biotechnology46: 1-10.
36.
Minkiewicz P., Dziuba J., Iwaniak A., Dziuba M. and Darewicz M. ( 2008b). BIOPEP database and other programs for processing bioactive peptide sequences. Journal of AOAC International91: 965-980.
37.
Miyoshi S., Ishikawa H., Kaneko T., Fukui F., Tanaka H. and Maruyama S. ( 1991). Structures and activity of angiotensin-converting enzyme inhibitors in an alpha-zein hydrolysate. Agricultural and Biological Chemistry55: 1313-1318.
38.
Muguerza E., Gimeno O., Ansorena D. and Astiasáran I. ( 2004). New formulations for healthier dry fermented sausages: A review. Trends in Food Science and Technology15: 452-457.
39.
Nagakura T., Yasuda N., Yamazaki K., Ikuta H., Yoshikawa S., Asano O. and Tanaka I. ( 2001). Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats. Biochemical and Biophysical Research Communications284: 501-506.
40.
Nochi T. and Kiyono H. ( 2006). Innate immunity in the mucosal immune system. Current Pharmaceutical Design12: 4203-4213.
41.
Nogata Y., Nagamine T., Yanaka M. and Ohta H. (2009). Angiotensin I converting enzyme inhibitory peptides produced by autolysis reactions from wheat bran. Journal of Agricultural and Food Chemistry57: 6618-6622.
42.
Ponda P.P. and Mayer L. ( 2005). Mucosal epithelium in health and disease. Current Molecular Medicine5: 549-556.
43.
Pripp A.H. ( 2005). Initial proteolysis of milk proteins and its effect on formation of ACE-inhibitory peptides during gastrointestinal proteolysis: a bioinformatic approach. European Food Research and Technology221: 712-716.
44.
Pripp A.H. ( 2008). Effect of peptides derived from food proteins on blood pressure: a meta-analysis of randomized controlled trials. Food and Nutrition Research52, http://www.foodandnutritionresearch.net/index.php/fnr/article/viewArticle/1641/1525 .
45.
Rawlings N.D. and Barrett A.J. ( 1999). MEROPS: The peptidase database. Nucleic Acids Research27: 325-331.
46.
Rawlings N.D., Morton F.R., Kok C.Y., Kong J. and Barrett A.J. ( 2008). MEROPS: the peptidase database. Nucleic Acids Research36: D320-D325.
47.
Salvatore T., Carbonara O., Cozzolino D., Torella R. and Sasso F.C. (2009). Progress in the oral treatment of type 2 diabetes: Update on DPP-IV inhibitors. Current Diabetes Reviews5: 92-101.
48.
Schomburg I., Chang A.J., Hoffmann O., Ebeling C., Ehrentreich F. and Schomburg D. ( 2002). BRENDA: a resource for enzyme data and metabolic information . Trends in Biochemical Sciences27: 54-56.
49.
Shahidi F. and Zhong Y. ( 2008). Bioactive peptides. Journal of AOAC International91: 914-931.
50.
Tanaka K.A., Key N.S. and Levy J.H. ( 2009). Blood coagulation: Hemostasis and thrombin regulation . Anesthesia and Analgesia108: 1433-1446.
51.
Tonouchi H., Suzuki M., Uchida M. and Oda M. ( 2008). Antihypertensive effect of an angiotensin converting enzyme inhibitory peptide from enzyme modified cheese. Journal of Dairy Research75: 284-290.
52.
Vanderheyden M., Bartunek J., Goethals M., Verstreken S., Lambeir A.-M., De Meester I. and Scharpé S. (2009). Dipeptidyl-peptidase IV and B-type natriuretic peptide. From bench to bedside. Clinical Chemistry and Laboratory Medicine47: 248-252.
53.
Vercruysse L., Smagghe G., van der Bent A., van Amerongen A., Ongenaert M. and Van Camp J. ( 2009). Critical evaluation of the use of bioinformatics as a theoretical tool to find high-potential sources of ACE inhibitory peptides . Peptides30: 575-582.
54.
Vercruysse L., Van Camp J. and Smagghe G. ( 2005). ACE inhibitory peptides derived from hydrolysates of animal muscle proteins. Journal of Agricultural and Food Chemistry53: 8106-8115.
55.
Vermeirssen V., van den Bent A., Van Camp J., van Amerongen A. and Verstraete W. ( 2004a). A quantitative in silico analysis calculates the angiotensin I converting enzyme (ACE) inhibitory activity in pea and whey protein digests . Biochimie86: 231-239.
56.
Vermeirssen V., Van Camp J. and Verstraete W. ( 2004b). Bioavailability of angiotensin I converting enzyme inhibitory peptides. British Journal of Nutrition92: 357-366.
57.
Wanasundara P.K.J.P.D., Ross A.R.S., Amarowicz R., Ambrose S.J., Pegg R.B. and Shand P.J. ( 2002). Peptides with angiotensin-converting enzyme (ACE) inhibitory activity from defibrinated, hydrolyzed bovine plasma. Journal of Agricultural and Food Chemistry50: 6981-6988.
58.
Yoshimoto T., Fischl M., Orlowski R.C. and Walter R. ( 1978). Post-proline cleaving enzyme and post-proline dipeptidyl aminopeptidase: comparison of two peptidases with high specificity for proline residues. Journal of Biological Chemistry253: 3708-3716.
