Navigation Links
Computational model simulates AZT metabolism in mitochondria

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 deoxynucleos ides, 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 Tech


Related biology news :

1. Supercomputer Dedicated To Bioengineering, Computational Biology Installed
2. Institute for Systems Biology Symposium Addresses Need for Better Computational Tools
3. Computational Method Speeds Mapping of Cell Signaling Networks
4. Computational verification of protein-protein interactions by orthologous co-expression
5. Computational Tool Predicts How Drugs Work In Cells, Advancing Efforts To Design Better Medicines
6. Computational analysis shows that plant hormones often go it alone
7. Scientists identify new model Of NK cell development
8. Genrate: a generative model that finds and scores new genes and exons in genomic microarray data
9. Molecular models advance the fight against malaria
10. NYU and MSKCC research provides model for understanding chemically induced cancer initiation
11. Genetic therapy reverses nervous system damage in animal model of inherited human disease
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/5/2017)... 5, 2017 Today HYPR Corp. , ... server component of the HYPR platform is officially ... end-to-end security architecture that empowers biometric authentication across Fortune ... already secured over 15 million users across the financial ... connected home product suites and physical access represent a ...
(Date:3/30/2017)... 30, 2017  On April 6-7, 2017, Sequencing.com will ... hackathon at Microsoft,s headquarters in ... focus on developing health and wellness apps that provide ... the Genome is the first hackathon for personal ... largest companies in the genomics, tech and health industries ...
(Date:3/28/2017)... -- The report "Video Surveillance Market by ... Devices), Software (Video Analytics, VMS), and Service (VSaaS, Installation ... 2022", published by MarketsandMarkets, the market was valued at ... reach USD 75.64 Billion by 2022, at a CAGR ... considered for the study is 2016 and the forecast ...
Breaking Biology News(10 mins):
(Date:6/22/2017)... ... 2017 , ... The first human cell line HeLa, established in 1951, has ... cross-contamination of human cell lines with HeLa cells were published. Until recently, cross-contamination and ... and is associated with dramatic consequences for research. , In this educational webinar, ...
(Date:6/22/2017)... MA (PRWEB) , ... June 22, 2017 , ... Charm ... ILVO validation. The AMPH test was determined to be appropriate as a screening test ... visual interpretation, on the Charm EZ system, and the Charm EZ Lite system. These ...
(Date:6/20/2017)... Florida (PRWEB) , ... June 20, 2017 , ... Biologist ... in men. While researching her latest book, Men Chase, Women Choose: The Neuroscience of ... that love has a physiological effect on men. ”The logical next step, in my ...
(Date:6/20/2017)... June 20, 2017  Kibow Biotech Inc., a pioneer ... the issuance of a new patent covering a unique ... the U.S. Patent and Trademark Office on May 23 ... the Buzz of Bio award in 2014 in ... developing non-drug approaches to chronic disease. Renadyl™, the first ...
Breaking Biology Technology: