Food Science and Biotechnology

  • 제14권6호
  • /
  • Pages.727-731
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  • 2005
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  • 1226-7708(pISSN)
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  • 2092-6456(eISSN)
한국식품과학회 (Korean Society of Food Science and Technology)
권호 표지

Hypocholesterolemic Soybean Peptide (IAVP) Inhibits HMG-CoA Reductase in a Competitive Manner

  • 발행 : 2005.12.31
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초록

Synthesized Ile-Ala-Val-Pro (IAVP) peptide, which has the highest hypocholesterolemic effect among a number of synthesized derivatives of Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA) isolated from 11S globulin of soy protein by pepsin digestion, was selected for investigation in the present study. Using a recombinant Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), we studied in detail the inhibition of this enzyme by IAVP and compared the action of this peptide to that of lovastatin, a known competitive inhibitor of this enzyme. The concentration of IAVP required for 50% inhibition ($IC_{50}$) of HMGR activity in given experimental conditions was $340\;{\mu}M$. Kinetic analysis revealed that the studied peptide is a competitive inhibitor of HMGR with respect to both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and nicotinamide adenine dinucleotide phosphate (NADPH), with an equilibrium constant of inhibitor binding ($K_i\;=\;[E][I]/[EI]$) of $61{\pm}1.2\;{\mu}M$ and $157{\pm}4.4\;{\mu}M$, respectively. At the same conditions, $K_i$ and $IC_{50}$ for lovastatin were $2.2{\pm}0.1\;nM$ and 12.5 nM, respectively. Thus, the given peptide interacts with HMGR as a bisubstrate, consequently blocking access of both substrates to the active sites. The achieved results suggest the design of new peptide sequences having a higher relative affinity to binding sites of this enzyme and an enhancement of their hypocholesterolemic properties.

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참고문헌

  1. J. Nutr. v.104 Factors affecting dry bean consumption in the United States Lucer, G.;Lin, B.;Allshouse, J.;Kantor, L.S.
  2. Nutr. Cancer v.125 Soybean phytoestrogen intake and cancer risk Adlercreutz, H.;Godlin, B.R.;Gorbach, S.L.;Hockerstedt, K.A.Y.;Watanabe, S.;Hamalalainen, E.K.;Markkanen, H.H.;Makela, T.H.;Wahala, K.T.;Hase, T.A.;Fotsis, T.
  3. Food Sci. Biotechnol v.12 Compositions of functional components of traditional Korean soybeans Kim, K.S.;Kim, M.J.;Park, J.S.;Sohn, H.S.;Kwon, D.Y.
  4. Atherosclerosis v.41 Long-term effects of semipurified diets containing casein or soy protein isolate on atherosclerosis and plasma lipoproteins in rabbits Huff, W.;Roberts, D.;Carroll, K.K.
  5. J. Am. Diet. Assoc. v.91 Review of clinical studies on cholesterol-lowering response to soy protein Carroll, K.K.
  6. New Eng. J. Med. v.333 Meta-analysis of effects of soy protein intake on serum lipids Anderson, J.W.;Johnstone, B.M.;Cook-Newell, M.E.
  7. Food Sci. Biotechnol. v.11 Amino acid substitution of hypocholesterolemic peptides originated from glycinin hydrolyzate Kwon, D.Y.;Oh, S.W.;Lee, J.S.;Yang, H.J.;Lee, S.H.;Lee, J.H.;Lee, Y.B.;Sohn, H.S.
  8. Chem. Nat. Comp. Isolation and identification ofhypocholesterolemic peptide from 11 S globulin of soy protein Pak, Y.V.;Koo, M.;Lee, N.;Lee, J.S.;Kasimova, T.D.;Kwon, D.Y.
  9. Chem. Nat. Comp. v.4 Conformation analysis of Ile-Ala-Yal-Pro peptide and its derivatives by circular dichroism Pak, V.V.;Koo, M.;Kasimova, T.D.;Kwon, D.Y.
  10. J. Biol.Chem. v.271 Regulation of 3-hydroxy3-methylglutaryl-coenzyme A reductase degradation by the nonsterol mevalonate metabolite famesol in vivo Meigs, T.E.;Roseman, R.S.;Simoni, R.D.
  11. J. Biol.Chem. v.267 Regulated degradation of 3-hydroxy-3methylglutaryl-coenzyme A reductase in permeabilized cells Meigs, T.E.;Simoni, R.D.
  12. Principles of Biochemistry Lehninger, A.L.;Nelson, D.L.;Cox, M.M.
  13. Protein Expression Purif. v.4 Syrian hamster 3hydroxy-3-methylglutaryl-coenzyme A reductase expression in Escherichia coli: Production of homogeneous protein Flimpong, K.;Damay, B.G.;Rodwell, V.W.
  14. Chem. Nat. Comp. v.41 Structure-activity relationship of Ile-Ala- Val-Pro peptide and its derivatives by using semi-empirical AMI method Pak, V.V.;Koo, M.;Lee, N.;Kim, M.S.;Kwon, D.Y.
  15. J. Org. Chem. v.37 The 9-fluorenyimethyloxycarbonyl aminoprotecting group Caprino, L.A.;Han, G.Y.
  16. Int. J. Pept. Protein Res. v.11 Solid-phase peptide synthesis using mild base cleavage of Na-fluorenylmethyloxycarbonyl-amino acids, exemplified by a synthesis of dihydrosomatostatin Chang, C.;Meienhofer, J.
  17. J. Mol. Biol. v.189 Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes Studier, F.W.;Moffatt, B.A.
  18. Anal. Biochem. v.72 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye-binding Bradford, M.M.
  19. Biochemical Calculations Segel, I.H.
  20. Biochemistry Voet, D.;Voet, J.G.
  21. Am. J. Cardiol. v.87 Preclinical and clinical pharmacology of rosuvastatin, a new 3-hydroxy- 3-methylglutaryl coenzyme A reductase inhibitor McTaggart, F.;Buckett, L.;Davidson, R.;Holdgate, G.;McCormick, A.;Schneck, D.;Smith, G.;Warwick, M.
  22. Atherosclerosis Suppl. v.4 Statin inhibition of HMG-CoA reductase: a 3dimensional view Istvan, E.S.
  23. Chem. Nat. Comp. v.41 Structures of the peptide Leu-Pro-Tyr-Pro and its derivatives and the nicotinamide part of NADPH by semi？empirical PM3 method Pak, V.V.;Koo, M.;Lee, N.;Kim, M.S.;Kasimova, T.D.;Kwon, D.Y.
  24. Biochim. Biophys. Acta v.1529 The structure of the catalytic portion of human NMG-CoA reductase Istvan, E.S.;Deisenhofer, J.
  25. EMBO J. v.19 Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis Istvan, E.S.;Palnitkar, M.;Buchanan, S.K.;Deisenhofer, J.