5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드

5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드
이름
IUPAC 이름
[(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
별칭
AICAR, Aminoimidazole carboxamide ribonucleotide, AICA ribonucleotide, ZMP, 5-Amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide
식별자
3D 모델 (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.019.285
KEGG
MeSH AICA+ribonucleotide
UNII
  • InChI=1S/C9H15N4O8P/c10-7-4(8(11)16)12-2-13(7)9-6(15)5(14)3(21-9)1-20-22(17,18)19/h2-3,5-6,9,14-15H,1,10H2,(H2,11,16)(H2,17,18,19)/t3-,5-,6-,9-/m1/s1 예
    Key: NOTGFIUVDGNKRI-UUOKFMHZSA-N 예
  • InChI=1/C9H15N4O8P/c10-7-4(8(11)16)12-2-13(7)9-6(15)5(14)3(21-9)1-20-22(17,18)19/h2-3,5-6,9,14-15H,1,10H2,(H2,11,16)(H2,17,18,19)/t3-,5-,6-,9-/m1/s1
    Key: NOTGFIUVDGNKRI-UUOKFMHZBG
  • O=P(O)(O)OC[C@H]2O[C@@H](n1cnc(C(=O)N)c1N)[C@H](O)[C@@H]2O
성질
C9H15N4O8P
몰 질량 338.213 g·mol−1
달리 명시된 경우를 제외하면, 표준상태(25 °C [77 °F], 100 kPa)에서 물질의 정보가 제공됨.
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5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드(영어: 5-aminoimidazole-4-carboxamide ribonucleotide, AICAR)는 퓨린 뉴클레오타이드 합성 과정에서의 대사 중간생성물이다. 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 AMP-의존성 단백질 키네이스(AMPK)의 활성을 자극할 수 있는 아데노신 일인산(AMP)의 유사체이다. 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 심장의 허혈성 손상을 치료하고 보호하기 위해 임상적으로 사용되어 왔다.[1] 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 수술 중에 심장으로 들어가는 혈류를 유지하는 방법으로 1980년대에 처음으로 사용되었다.[2] 현재 AICAR은 근육의 물리적 구성을 변화시켜 조직의 대사 활성을 증가시킴으로써 당뇨병의 잠재적 치료제로도 보여지고 있다.[3]

작용 기작

5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드의 뉴클레오사이드 형태인 아카데신은 심장 세포로 들어가서 아데노신 키네이스와 아데노신 탈아미노효소를 저해하는 아데노신의 유사체이다. 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 심근의 허혈 상태에서만 아데노신 일인산으로부터 아데노신의 생성을 증가시키는 뉴클레오타이드 재합성 속도를 증가시킨다.[4] 심장근육세포에서 아카데신은 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드로 인산화되어 뉴클레오타이드의 수준을 변화시키지 않고 AMP-의존성 단백질 키네이스를 활성화시킨다.[5] 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 아데노신 합성을 위한 신생합성 경로로 들어가서 ATP의 수준과 아데노신의 수준을 증가시키는 아데노신 탈아미노효소를 저해할 수 있다.[6]

의료용

장기간의 허혈에 앞서 재관류를 동반한 짧은 기간의 관상동맥 폐색은 허혈성 전처치로 알려져 있다. 이것은 보호적인 것으로 나타났다. 전처치는 심근 경색보다 앞서서 재관류 요법을 통해 심근 경색을 막고 세포 사멸을 지연시킬 수 있다.[7] 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 허혈 직전이나 허혈 중인 심장을 전처치하는 것으로 나타났다.[8] 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 내피의 산화 질소 합성효소로부터 일산화 질소(NO)의 생성을 증가시킴으로써 전처치된 항염증 상태를 유발시킨다.[9] 재관류 24시간 전에 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드를 투여하면 일산화 질소 생성 증가와 함께 허혈성 백혈구-내피 세포 접착 상호작용을 방지한다.[10] 또한, 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드-의존적 전처치는 ATP-민감성 칼륨 통로 및 헴옥시제네이스-의존적 기작에 의해 매개된다. 이는 ATP-민감성 칼륨 통로의 AMP-의존적 단백질 키네이스-의존적 반응을 증가시켜 활동 전위의 지속 시간을 단축시키고 재관류 중 칼슘 과부하를 방지한다.[11] 칼슘 과부하의 감소는 활성 산소에 의한 염증의 활성화를 방지한다.[12] 또한, 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 허혈성 재관류 후 심장에 이로운 GLUT4의 위치 변경을 통해 AMP-활성 단백질 키네이스-의존적 포도당 흡수를 증가시킨다.[13] 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드 전처치 동안 포도당의 증가는 토끼에서 최대 2시간까지, 관상동맥 수술 중인 사람에서 40분까지 전처치하는 시간을 연장시킨다.[7][14] 결과적으로, 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 사람에서 심근 경색의 빈도와 크기를 최대 25%까지 감소시켜 심장으로의 혈액의 흐름을 개선시킨다.[7][15] 또한, 이러한 치료법은 허혈성 손상으로 인한 조기 사망의 위험을 줄이고 수술 후 회복을 개선시키는 것으로 나타났다.[7]

운동 능력 향상 약물로 사용

2009년에 프랑스 반도핑기구는 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드가 2009 투르 드 프랑스에서 운동능력 향상 약물로 사용된 것으로 추정된다고 의심했다.[16][17] 세계 반도핑기구에 탐지 방법이 주어진 것으로 알려졌지만, 이 방법이 시행됐는지는 알려지지 않았다.[18] 2011년 1월에 5-아미노이미다졸-4-카복사마이드 리보뉴클레오타이드는 세계 반도핑규약에서 공식적으로 금지된 물질이었으며,[19] 엘리트 선수들의 표준 수준이 결정되어 검사 결과를 해석하고 있다.[20]

같이 보기

각주

  1. Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 229:558–565(1995)
  2. Galinanes M, Bullough D, Mullane KM, Hearse DJ. Sustained protection by acadesine against ischemia- and reperfusion-induced injury. Studies in the transplanted rat heart.Circulation 86:589–597 (1992)
  3. Zarembo, Alan. "'Exercise pill' could take the work out of workouts." Los Angeles Times. 01 08 2008, n. pag. Web. 21 Jan. 2012.
  4. Kristiansen, S.B. et al. 5-Aminoimidazole-4-carboxamide-1- β - d -ribofuranoside Increases Myocardial Glucose Uptake during Reperfusion and Induces Late Pre-conditioning : Potential Role of AMP-Activated Protein Kinase. Pharmacology Toxicology 10-16 (2009).doi:10.1111/j.1742-7843.2009.00402.x
  5. Zhang, L., Frederich, M., He, H., & Balschi, J. a. Relationship between 5-aminoimidazole-4-carboxamide-ribotide and AMP-activated protein kinase activity in the perfused mouse heart. American Journal of Physiology. Heart and circulatory physiology, 290(3), .H1235-43. (2006)doi:10.1152/ajpheart.00906.2005
  6. Longnus SL, Wambolt RB, Parsons HL, Brownsey RW, Allard MF 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms. Am J Physiol Regul Integr Comp Physiol 284:R936–R944 (2003)
  7. Murry, C.E., Jennings, R.B. & Reimer, K.A.. Preconditioning with ischaemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124–1136. (1986)
  8. Mullane K Acadesine: the prototype adenosine regulating for reducing myocardial ischaemic injury. Cardiovasc Res 27:43–47(1993)
  9. Gaskin, F. Spencer. "MECHANISMS OF ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN KINASE-INDUCED PRECONDITIONING IN ISCHEMIA/REPERFUSION." Department of Medical Pharmacology and Physiology. (2007)
  10. F. Spencer Gaskin, Kazuhiro Kamada, Mozow Yusof, William Durante, Garrett Gross, and Ronald J. Korthuis. AICAR Preconditioning Prevents Postischemic Leukocyte Rolling and Adhesion: Role of KATP Channels and Heme Oxygenase Microcirculation 16:2, 167-176 (2009)
  11. Sukhodub, A., Jovanovic, S., Du, Q., Budas, G., Clelland, A.K., Shen, M., Sakamoto, K., Tian, R. & Jovanovic, A. AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive K(+) channels. J Cell Physiol 210, 224–236. (2007).
  12. Tsuchida, A., Yang, X.M., Burckhartt, B., Mullane, K.M., Cohen, M.V. & Downey, J.M. Acadesine extends the window of protection afforded by ischaemic preconditioning. Cardiovasc Res 28, 379–383. (1994).
  13. Iii, R.R.R. et al. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Society (2012).
  14. Burckhartt, B., Yang, X.M., Tsuchida, A., Mullane, K.M., Downey, J.M. & Cohen, M.V. Acadesine extends the window of protection afforded by ischaemic preconditioning in conscious rabbits. Cardiovasc Res 29, 653–657. (1995).
  15. Mangano DT. Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis Pflügers Arch - Eur J Physiol (2006) 453:147–156 155 of the 5 international randomized trials. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group. JAMA 277:325–332(1997)
  16. Cooke, Nicole. “CIRC report is admirable but authorities must do more on drugs”. The Guardian. 2015년 3월 13일에 확인함. There will always be new drugs, such as the weight-loss drug Aicar, which enables riders to shed up to 7kg and yet still maintain their power output. Obviously, it takes time to develop tests for these but it needs to be agreed that retrospective testing can secure sanctions. 
  17. Niiler, Eric. “Doping Spreading to Amateur Cyclists: Report”. Discovery. 2015년 5월 11일에 원본 문서에서 보존된 문서. 2015년 3월 13일에 확인함. The commission, formed in 2013 by the sport's governing body, interviewed 174 experts, riders, doctors and team officials. It found a flood of new substances or methods used to enhance blood oxygen capacity include Aicar, Xenon gas, ozone therapy, ITPP, Gas6, Actovegin, various forms of EPO such as CERA, "Eprex", EPO zeta, EPO Retacrit, Neorecormon, and Albumina. Most of these are used to help patients with severe anemia or blood disorders. 
  18. “AFLD president suspects new drugs in peloton”. 《Cyclingnews》. Future Publishing Unlimited. 2009년 7월 27일. 2012년 3월 17일에 확인함. 
  19. “Important changes made to the World Anti-Doping Code”. 《Cyclingnews》. Future Publishing Unlimited. 2010년 12월 20일. 2012년 3월 17일에 확인함. 
  20. “CYCLING INDEPENDENT REFORM COMMISSION” (PDF). 2015년 3월 13일에 확인함. The core elements to achieve performance enhancement through doping in cycling have remained the same over the years: firstly, increasing the blood’s oxygen carrying capacity, and, secondly, stimulating muscle growth and aiding muscle recovery. Over the years riders have adapted the substances and methods used to achieve these goals in response to: (i) the type of substances available and accessible on the pharmaceutical market (e.g., various EPO generations); (ii) specific drug detection capabilities of laboratories, (e.g., the switch from EPO to blood transfusions or to ozone therapy, or even towards the so-called “oxygen in a pill” in the form of GW1516 and AICAR); and (iii) other anti-doping tools, such as the ABP which has led to micro-dosing (see below). 

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Shahrbanoo Sadat Información personalNombre en persa شهربانو سادات Nacimiento 1990 Teherán (Irán) Nacionalidad AfganaInformación profesionalOcupación Guionista, directora de cine y cineasta [editar datos en Wikidata] Shahrbanoo Sadat y Anwar Hashimi en el IFFR 2020 promoviendo la película El orfanato. Shahrbanoo Sadat (en persa, شهربانو سادات) ( Teherán, 1990), es una guionista, productora y directora de cine afgana.[1]​ Biografía Originaria de ...

This article includes a list of references, related reading, or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (August 2019) (Learn how and when to remove this template message) The Intercollegiate Prohibition Association was established in Chicago, Illinois, in 1901 and by 1903 was reported to be the largest college organization in the United States. It conducted an inquiry among 158...

 

Текст із манускрипту Войнича Рукопис Войнича Рукопис Войнича (англ. Voynich Manuscript) — ілюстрований рукопис (кодекс), написаний невідомим письмом. Таку назву книга отримала через американського книготорговця польського походження, вихідця з території сучасної Литви Вілфр...

 

Art Nouveau building in the Lypky neighborhood of Kyiv, Ukraine House with ChimaerasThe front façade of the House with ChimaerasGeneral informationArchitectural styleArt NouveauLocationLypky, Kyiv, UkraineAddress10 Bankova StreetCoordinates50°26′42″N 30°31′43″E / 50.44500°N 30.52861°E / 50.44500; 30.52861Construction started1901Completed1902Technical detailsStructural systemConcrete pilesContinuous foundationFloor count3 (Bankova) 6 (Franko Square)Floor ar...

Local election 2019 Rushmoor Borough Council election ← 2018 2 May 2019 2021 → 13 seats of 39 to Rushmoor Borough Council20 seats needed for a majority   First party Second party Third party   Party Conservative Labour Liberal Democrats Seats before 25 11 1 Seats won 9 3 1 Seats after 26 11 2 Seat change Popular vote 8,239 5,798 2,162 Results by Ward Council control before election Conservative Council control after election Conservativ...

 

Otto Sonnenholzner Vicepresidente de la República del Ecuador 11 de diciembre de 2018-17 de julio de 2020Presidente Lenín MorenoPredecesora María Alejandra VicuñaSucesora María Alejandra Muñoz Información personalNacimiento 19 de marzo de 1983 (41 años)Guayaquil (Guayas, Ecuador) Nacionalidad EcuatorianaLengua materna Español FamiliaPadres Ramón Sonnenholzner Rosa Elena Sper Cónyuge Claudia Salem Barakat (m.2008)Hijos 3 EducaciónEducado en Colegio Alemán Humboldt Guayaquil (...

 

Strategi Solo vs Squad di Free Fire: Cara Menang Mudah!