Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effects of Transglycoslyation Products of Soy Isoflavones on Cholesterol Biosynthesis

대두 이소플라본 당전이 반응 산물의 콜레스테롤 생합성 저해 효과

  • Yoo, Lang Kuk (Department of Agricultural Biotechnology, Seoul National University) ;
  • Choi, Seung Jun (Department of Food Science and Technology, Seoul National University of Science and Technology) ;
  • Moon, Tae Wha (Department of Agricultural Biotechnology, Seoul National University) ;
  • Shim, Jae-Hoon (Department of Food Science and Nutrition, Hallym University)
  • 유랑국 (서울대학교 농생명공학부) ;
  • 최승준 (서울과학기술대학교 식품공학과) ;
  • 문태화 (서울대학교 농생명공학부) ;
  • 심재훈 (한림대학교 식품영양학과)
  • Received : 2015.08.13
  • Accepted : 2015.09.25
  • Published : 2016.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

Hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) is the rate-limiting enzyme in biosynthesis of cholesterol in animals. In this study, inhibitory effects of isoflavone glycosides on HMG-CoA reductase were investigated. At sample concentration of $100{\mu}M$, genistein-7-O-triglucoside (G2-genistin) inhibited HMG-CoA reductase activity by approximately 18%, whereas daidzein-7-O-triglucoside had no inhibitory effect. In the kinetic experiments with Syrian hamster HMG-CoA reductase, G2-genistin showed inhibitory efficacy with an invariable $V_{max}$ value, suggesting that G2-genistin works as a competitive inhibitor of HMG-CoA reductase and has potential for hypocholesterolemic action through direct regulation of HMG-CoA reductase.

HMG-CoA reductase는 체내 콜레스테롤 생합성에 있어서 속도제한단계(율속) 효소이다. 본 연구는 HMG-CoA reductase에 대한 이소플라본 배당체의 저해 효과를 연구하였다. $100{\mu}M$의 농도에서 genistein-7-O-triglucoside(G2-genistin)는 HMG-CoA reductase 활성을 약 18% 정도 저해하였으나, daidzein-7-O-triglucoside는 저해 효과를 갖지 않았다. 시리아햄스터 HMG-CoA reductase의 반응속도 실험에서 G2-genistin은 농도에 관계없이 $V_{max}$의 저해 정도가 일정하였으며, 이것은 G2-genistin이 HMG-CoA reductase의 경쟁적 저해제로 작용함을 시사하고 HMG-CoA reductase의 활성을 직접적으로 저해함으로써 혈중 콜레스테롤 함량을 감소시킬 수 있음을 예상할 수 있다.

Keywords

References

  1. Anthony MS. 2000. Soy and cardiovascular disease: cholesterol lowering and beyond. J Nutr 130: 662S-663S. https://doi.org/10.1093/jn/130.3.662S
  2. Choi YS, Kim JH, Yoon DH. 2002. Effects of soy extract and sex on serum and liver lipid levels of the rat. Food Sci Biotechnol 11: 10-13.
  3. Lichtenstein AH. 2001. Potential benefits of soy protein in managing patients with hypercholesterolemia. Nutr Clin Care 3: 139-144.
  4. Nagata C. 2000. Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan. Int J Epidemiol 29: 832-836. https://doi.org/10.1093/ije/29.5.832
  5. Wong WW, Smith EO, Stuff JE, Hachey DL, Heird WC, Pownell HJ. 1998. Cholesterol-lowering effect of soy protein in normocholesterolemic and hypercholesterolemic men. Am J Clin Nutr 68: 1385S-1389S. https://doi.org/10.1093/ajcn/68.6.1385S
  6. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. 2000. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72: 844-852. https://doi.org/10.1093/ajcn/72.3.844
  7. Somekawa Y, Chiguchi M, Ishibashi T, Aso T. 2001. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 97: 109-115.
  8. Boue SM, Wiese TE, Nehls S, Burow ME, Elliott S, Carter-Wientjes CH, Shih BY, McLachlan JA, Cleveland TE. 2003. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J Agric Food Chem 51: 2193-2199. https://doi.org/10.1021/jf021114s
  9. Kapiotis S, Hermann M, Held I, Seelos C, Ehringer H, Gmeiner BM. 1997. Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Arterioscler Thromb Vasc Biol 17: 2868-2874. https://doi.org/10.1161/01.ATV.17.11.2868
  10. Anderson JJB, Garner SC. 1997. The effects of phytoestrogens on bone. Nutr Rev 17: 1617-1632.
  11. Adlercreutz CH, Goldin BR, Gorbach SL, Hockerstedt KA, Watanabe S, Hamalainen EK, Markkanen MH, Makela TH, Wahala KT, Adlercreutz T. 1995. Soybean phytoestrogen intake and cancer risk. J Nutr 125: 757S-770S.
  12. Wangen KE, Duncan AM, Xu X, Kurzer MS. 2001. Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Am J Clin Nutr 73: 225-231. https://doi.org/10.1093/ajcn/73.2.225
  13. Sung JH, Choi SJ, Lee SW, Park KH, Moon TW. 2004. Isoflavones found in Korean soybean paste as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Biosci Biotechnol Biochem 68: 1051-1058. https://doi.org/10.1271/bbb.68.1051
  14. Sung JH, Lee SJ, Park KH, Moon TW. 2004. Isoflavones inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase in vitro. Biosci Biotechnol Biochem 68: 428-432. https://doi.org/10.1271/bbb.68.428
  15. Li D, Park JH, Park JT, Park CS, Park KH. 2004. Biotechnological production of highly soluble daidzein glycosides using Thermotoga maritima maltosyltransferase. J Agric Food Chem 52: 2561-2567. https://doi.org/10.1021/jf035109f
  16. Li D, Park SH, Shim JH, Lee HS, Tang SY, Park CS, Park KH. 2004. In vitro enzymatic modification of puerarin to puerarin glycosides by maltogenic amylase. Carbohydr Res 339: 2789-2797. https://doi.org/10.1016/j.carres.2004.09.017
  17. Li D, Roh SA, Shim JH, Mikami B, Baik MY, Park CS, Park KH. 2005. Glycosylation of genistin into soluble inclusion complex form of cyclic glucans by enzymatic modification. J Agric Food Chem 53: 6516-6524. https://doi.org/10.1021/jf050732g
  18. Chung MJ, Kang AY, Lee KM, Oh E, Jun HJ, Kim SY, Auh JH, Moon TW, Lee SJ, Park KH. 2006. Water-soluble genistin glycoside isoflavones up-regulate antioxidant metallothionein expression and scavenge free radicals. J Agric Food Chem 54: 3819-3826. https://doi.org/10.1021/jf060510y
  19. Frimpong K, Darnay BG, Rodwell VW. 1993. Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase expressed in Escherichia coli: production of homogeneous protein. Protein Expr Purif 4: 337-344. https://doi.org/10.1006/prep.1993.1044
  20. Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254. https://doi.org/10.1016/0003-2697(76)90527-3
  21. Breton M, Precigoux G, Courseille C, Hospital M. 1975. Genisteine. Acta Crystallogr Sect B 31: 921-923. https://doi.org/10.1107/S056774087500413X