Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tryptophan deficiency may underlie quinine side effects

30.06.2009
Researchers have found that the anti-malarial drug quinine can block a cell's ability to take up the essential amino acid tryptophan, a discovery that may explain many of the adverse side-effects associated with quinine. Once confirmed, these findings would suggest that dietary tryptophan supplements could be a simple and inexpensive way to improve the performance of this important drug.

Quinine is a very commonly used anti-malarial drug, yet to this day the principal mode of quinine action against the malaria parasite is still largely unclear, as is the basis for adverse reactions like nausea, headaches, and blurred vision.

To address these gaps, Simon Avery and colleagues at the University of Nottingham took advantage of yeast genetics, examining the effects of quinine on a collection of 6000 yeast mutants, each one lacking exactly one of the yeast's 6000 genes. While quite different from humans, yeast is comparable on a cellular level and yeast is frequently, and successfully, used as front-line agents in testing chemicals and small molecule drugs.

Their screen revealed that strains unable to make tryptophan were extremely susceptible to quinine poisoning, which led them to identify a tryptophan transporter as a key quinine target (yeast that cannot make their own tryptophan have to rely exclusively on external sources, and thus die if tryptophan transport is blocked).

This discovery fits in well with evidence that quinine reactions are more severe in malnourished individuals. Unlike yeast, humans cannot make their own tryptophan and thus require dietary tryptophan, which is abundant in meat but limited in yams, a staple food crop in the tropics where malaria is prevalent. If quinine severely reduces tryptophan uptake, then it follows that people with preexisting tryptophan deficiencies would be especially at risk to this drug.

The authors also note that tryptophan is important as a precursor for the brain chemical serotonin, so the enhanced tryptophan deficiency induced by quinine could explain why many of quinine's side effects are localized to the head region. They also note that side-effects could be averted simply by taking dietary tryptophan supplements in conjunction with quinine treatments, though it is not yet known if tryptophan may affect quinine action against the malaria parasite.

This study appears in the July 3rd issue of Journal of Biological Chemistry and will be published online June 26.

From the Article: "THE ANTIMALARIAL DRUG QUININE DISRUPTS TAT2P-MEDIATED TRYPTOPHAN TRANSPORT AND CAUSES TRP STARVATION" by Combiz Khozoie, Richard J. Pleass and Simon V. Avery

Article link: http://www.jbc.org/cgi/content/abstract/M109.005843v1

Corresponding Author: Simon Avery, Institute of Genetics, University of Nottingham, U.K. Tel: +44-115-951-3315, email: Simon.Avery@nottingham.ac.uk

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 12,000 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

Nick Zagorski | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

nachricht Tiny Helpers that Clean Cells
14.08.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

Tiny Helpers that Clean Cells

14.08.2018 | Life Sciences

Algorithm provides early warning system for tracking groundwater contamination

14.08.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>