DOI QR코드

DOI QR Code

Inhibition of Diacylglycerol Acyltransferase by Phenylpyropenes Produced by Penicillium griseofulvum F1959

  • Lee, Seung-Woong (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Rho, Mun-Chual (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Choi, Jung-Ho (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Koan-Hoi (Department of Pharmacology, Pusan National University-School of Medicine) ;
  • Choi, Yong-Seok (School of Life Sciences and Biotechnology, Korea University) ;
  • Lee, Hyun-Sun (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Young-Kook (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • 발행 : 2008.11.30

초록

Phenylpyropenes A, B, and C, isolated from Penicillium griseofulvum F1959, inhibited DGAT in rat liver microsomes with $IC_{50}$ values of $78.7{\pm}1.6$, $21.7{\pm}0.2$, and $11.04{\pm}0.2{\mu}M$, respectively. In addition, a kinetic analysis using a Lineweaver-Burk plot revealed that phenylpyropene C was a noncompetitive inhibitor of DGAT. The apparent Michaelis constant ($K_m$) value and inhibition constant ($K_i$) value were calculated to be $8{\mu}M$ and $10.48{\mu}M$, respectively. Moreover, phenylpyropene C inhibited triglyceride formation in HepG2 cells.

키워드

참고문헌

  1. Bell, P. M. and R. A. Coleman. 1980. Enzymes of glycerolipid synthesis in eukaryotes. Annu. Rev. Biochem. 19: 459-487
  2. Cases, S., S. J. Smith, Y. W. Zheng, H. M. Myers, S. R. Lear, E. Sande, et al. 1998. Identification of a gene encoding an acyl CoA: Diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc. Natl. Acad. Sci. USA 95: 13018-13023
  3. Chen, H. C., S. J. Smith, Z. Ladha, D. R. Jenson, L. D. Ferreira, L. K. Pulawa, et al. 2002. Increased insulin and leptin sensitivity in mice lacking acyl CoA: Diacylglycerol acyltransferase 1. J. Clin. Invest. 109: 1049-1055 https://doi.org/10.1172/JCI0214672
  4. Chung, M. Y., M. Rho, J. S. Ko, S. Y. Ryu, K. H. Jeune, K. Kim, H. S. Lee, and Y. K. Kim. 2004. In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens. Planta Med. 70: 258-260 https://doi.org/10.1055/s-2004-815545
  5. Coleman, R. A. 1992. Diacylglycerol acyltransferase and monoacylglycerol acyltransferase from liver and intestine. Methods Enzymol. 209: 98-103 https://doi.org/10.1016/0076-6879(92)09013-S
  6. Kwon, O. E., M. C. Rho, H. Y. Song, S. W. Lee, M. Y. Chung, J. H. Lee, Y. H. Kim, H. S. Lee, and Y. K. Kim. 2002. Phenylpyropene A and B, new inhibitor of acyl-CoA: Cholesterol acyltransferase produced by Penicillium griseofulvum F1959. J. Antibiot. 55: 1004-1008 https://doi.org/10.7164/antibiotics.55.1004
  7. Lehner, R. and A. Kuksis. 1996. Biosynthesis of triacylglycerols. Prog. Lipid Res. 35: 169-201 https://doi.org/10.1016/0163-7827(96)00005-7
  8. Rho, M. C., H. S. Lee, K. T. Chang, H. Y. Song, O. E. Kwon, S. W. Lee, J. S. Ko, S. G. Hong, and Y. K. Kim. 2002. Phenylpyropene C, a new inhibitor of acyl-CoA: Cholesterol acyltransferase produced by Penicillium griseofulvum F1959. J. Antibiot. 55: 211-214 https://doi.org/10.7164/antibiotics.55.211
  9. Smith, S. J., S. Cases, D. R. Jenson, H. C. Chen, E. Sande, B. Tow, et al. 2000. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT. Nat. Genet. 25: 87-90 https://doi.org/10.1038/75651
  10. Tomoda, H., K. Igarashi, J. C. Cyong, and S. Omura. 1991. Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation. J. Biol. Chem. 266: 4214-4219
  11. Yu, Y. and H. Ginsberg. 2004. The role of acyl-CoA: Diacylglycerol acyltransferase (DGAT) in energy metabolism. Annu. Rev. Med. 36: 252-261 https://doi.org/10.1080/07853890410028429

피인용 문헌

  1. Triacylglycerol synthesis and energy metabolism: a gut reaction? vol.4, pp.6, 2008, https://doi.org/10.2217/clp.09.67
  2. Therapeutic Strategies for Metabolic Diseases: Small-Molecule Diacylglycerol Acyltransferase (DGAT) Inhibitors vol.9, pp.11, 2008, https://doi.org/10.1002/cmdc.201402069