Cardiovascular and Metabolic Disease Center
Mitochondrial Research Affinity Collaboration-Laboratories & Engineering

Home > 0

Computational Model Simulates AZT Metabolism In Mitochondria

  • 작성자한진
  • 작성일2006-07-27 09:59:31
  • 조회수2086
  • 첨부파일첨부파일
7/24/2006 Blacksburg, VA - Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have developed a computational model that allows scientists to better understand the metabolism and toxicity of the HIV/AIDS drug zidovudine (azidothymidine, AZT). AZT is used successfully as part of Highly Active Anti-Retroviral Therapy (HAART) to control the level of the human immunodeficiency virus in HIV-infected individuals. However, long-term use of AZT may lead to side-effects in some patients. David Samuels and coworkers are interested in finding out whether the toxic side effects of AZT can eventually be minimized or even eliminated. For this purpose, they have been developing a detailed computational model that allows scientists to simulate the biochemical reactions that take place when AZT is metabolized in cells, including their mitochondria, under different metabolic conditions. Drugs like AZT may interfere with DNA replication in the mitochondria, the energy factories of our cells, and can lead to potentially fatal side effects in patients undergoing HAART treatment. Samuels, assistant professor at VBI, commented: "HAART is one of the biggest success stories in modern medicine. The goal of our work is to help improve this successful treatment by understanding the toxic effects that AZT can have in some people. There are many different ways that AZT could possibly interfere with mitochondria to cause the toxic side-effects. Our job is to model these proposed toxicity mechanisms to see which ones could actually lead to the mitochondrial defects found in AIDS patients." He added: "It is possible that no single mechanism is responsible for the toxicity, but that instead a combination of multiple effects is needed. That is the kind of problem that needs a systems biology approach." When AZT reaches a cell, it is subject to some of the same metabolic modifications or phosphorylation events that are encountered by the four naturally occurring deoxynucleosides, the building blocks used to make DNA. However, modified AZT molecules lack a specific chemical group (a hydroxyl group) that would allow DNA replication to continue. This results in premature termination of DNA synthesis. It is thought that the triphosphorylated form of AZT can enter the mitochondrial matrix, the inner core of the mitochondrion, and disrupt the replication of mitochondrial DNA by prematurely terminating DNA synthesis. Samuels added: "We're just starting our work. It is too early to say what the mechanism of mitochondrial toxicity of AZT is. The inhibition of deoxynucleoside metabolism is one possibility. The incorporation of AZT into mitochondrial DNA is another." He added: "The detailed computational model that we have developed should allow researchers to explore different hypotheses as to why AZT can lead to such debilitating side effects in some patients undergoing anti-retroviral treatment." SOURCE: Virginia Bioinformatics Institute
Total404 [ page1/27 ]
No. 제목 작성자 작성일 조회수
404 인제대, 과기정통부 ‘2023년도 기초연구실 지원사업’ 선정 2023.09.13 관리자 (web_admin) 2023.09.13 11
403 인제대 교수팀 '돌연사 주범 심부전 원인 규명' 2023.09.13 관리자 (web_admin) 2023.09.13 11
402 2022학년도 인제학술상 수상자 선정 결과 2023.01.05 관리자 2023.01.05 63
401 안전관리 우수연구실 인증 취득 2023.01.05 관리자 2023.01.05 41
400 한진교수 화의자의학상 수상 2023.01.05 관리자 2023.01.05 60
399 이온통로 학회 -Amy 포스터상 수상 2019.01.15 김형규 2019.01.15 2,587
398 센터 겸임교수 조성우 교수 - 한빛사 -JACC Vascular Imaging 2018.12.08 김형규 2018.12.08 2,791
397 2017 IMPACT Symposium 개최 첨부파일 2017.10.31 김보현 2017.10.31 2,588
396 경암바이오유스 2017 첨부파일 2017.08.11 김보현 2017.08.11 2,871
395 KORUS 2017 첨부파일 2017.06.21 김보현 2017.06.21 2,986
394 IMPACT 2016 심포지엄 개최 안내 첨부파일 2016.04.18 관리자 2016.04.18 4,003
393 IMPACT 2015 심포지엄 개최 안내 첨부파일 2015.04.20 서대윤 2015.04.20 2,869
392 2015 중점연구소 성과 전시회 첨부파일 2015.03.31 김형규 2015.03.31 2,462
391 Best Miso Award - 한진 2014.11.04 이정훈 2014.11.04 2,072
390 신진생리학자상 - 김형규 2014.10.29 이정훈 2014.10.29 1,816
처음이전1 2 3 4 5 6 7 8 9 10 다음 마지막