[의학]AMPK

소개

1. what is AMPK
2. structure of AMPK
3. regulatin of AMPK activity
4. contraction-induced activation of AMPK in muscle
5. regulation of muscle fatty acid oxidation by AMPK
6. Role in glucose uptake
7. role in control of GLUT-4 and hexokinase
8. role in control of mitochondrial protein
9. A contributory factor in the obesity could be dysregulation of the malonyl CoA-AMPK fuel-sensing and signaling network

목차

1. what is AMPK
2. structure of AMPK
3. regulatin of AMPK activity
4. contraction-induced activation of AMPK in muscle
5. regulation of muscle fatty acid oxidation by AMPK
6. Role in glucose uptake
7. role in control of GLUT-4 and hexokinase
8. role in control of mitochondrial protein
9. A contributory factor in the obesity could be dysregulation of the malonyl CoA-AMPK fuel-sensing and signaling network

본문내용

• AMPK system is activated by
- allosteric mechanism
- covalent mechanism

• AMPK activation mechanism
① allosteric activation of AMPK by AMP
② covalently activation of the upstream kinase, AMPKK, by AMP
③ binding of AMP to AMPK, making it a better substrate for AMPKK
④ binding of AMP to AMPK , making it a worse substrate for protein phosphatases

⇒ >200-fold activation and results in the system being exquisitely sensitive to small changes in AMP concentration in the cell
• AMPK system responds to the AMP/ATP rather than just to the level of AMP
- AMP & ATP vary reciprocally in cells because of the action of adenylate
kinase(myokinase)
- device to increase the sensitivity of the system
- allosteric & covalent

• AMPK activity is modulated by the PCr : Cr ratio
- entirely allosteric

참고자료

· Department of Zoology, Brigham young University, Provo, Utah 84602.Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle. J Appl Physiol 91;1017-1028,2001
· Cheung PDF, Salt IP, Davies SP, Hardie DG, and Carling D. Characterization of AMP-activated protein kinase ϒ-subunit isoforms and their role in AMP binding. Biochem J 346: 659-669,2000
· D. Grahame Hardie. J. Clin. Invest. 114:465-468 (2004).
· Aschenbach WG, Sakamoto K, Goodyear LJ.  5` adenosine monophosphate-activated protein kinase, metabolism and exercise. Sports Med. 2004;34(2):91-103.
· Kawanaka K, Nolte LA, Hansen PA, and Holloszy JO. Mechanisms underlying impaired GLUT-4 translocation in glycogen supercompensated muscles of exercised rats. Am J Physiol Endocrinol Metab 279:E1311-E1318,2000
· Vavvas D, Apazidis A, Saha AK, Gamble J, Patel A, Kemp BE, Witters LA, and Ruderman NM. Contraction-induced changes in acetyl-CoA carboxylase and 5’-AMP-activated kinase in skeletal muscle. J Biol Chem 272 : 13256-13261,1997.
· 7. Hayashi T, Hirshman MF, Fugii N, Habinowski SA, Witters LA, and Goodyear LJ. Metabolic stress and altered glucose transport. Activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 49:527-531,2000
· 8. Zheng D, MacLean PS, Pohnert SC, Knight JB, Olson AL, Winder WW, and Dohm GL. Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. J Appl Physiol In press
· 9. Ojuka EO, Nolte LA, and Holloszy JO.Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro.J Appl Physiol. 2000 Mar;88(3):1072-5.
· 10. Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, and Holloszy JO. Activation of AMP-acitvated protein kinase increases mitochobdrial enqymes in skeletal muscle. J Appl Physiol 88:2219-2226,2000.
· 11. Winder WW and Hardie DG. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol Endocrinol Metab 277:E1-E10, 1999
· 12. Ponticos, M.,Q.L.Lu,J.E.Morgan, D.G.Hardie, T.A.Partridge, and D.Carling. Dual regualtion of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle. EMBO J. 17:1688-1699,1998.