Malarial parasite breaks amino acid

21 Feb 2009, 1031 hrs IST, ANI

WASHINGTON: Malarial parasite breaks down an important amino acid, called arginine, in a bid to adapt and thrive within the human body, according
to researchers from Princeton University and the Drexel University College of Medicine. It was found that the parasite might trigger a more critical and deadlier phase of the disease by depleting arginine.

According to the scientists, understanding of this aspect of malaria metabolism can provide new insights on the interactions between the parasite and its human hosts. Also, the finding may pave way for better treatments. "The more we know about the parasite's metabolic network, the more intelligent we can be about targeting therapies that will cure malaria," said Kellen Olszewski, a graduate student at Princeton University and first author of the study.

Manuel Llinas, an assistant professor of molecular biology and the Lewis-Sigler Institute led the project for Integrative Genomics at Princeton. For the study, scientists created a "metabolomic" profile of the parasite, Plasmodium falciparum. Metabolomics is a new field that aims to analyse metabolic processes by simultaneously measuring the levels of all of the more than 500 core metabolites that make up an organism's "metabolic network."

The researchers used a mass spectrometry, which is a highly sensitive technique that identifies chemicals based on their size and electrical charge. They wanted to see how the concentrations of metabolites in parasite-infected human red blood cells change over a single 48-hour "generation" of parasite growth.

Scanning the data, the scientists noted that arginine levels dramatically dipped by the end of one 48-hour cycle. "The parasite destroys this amino acid specifically and preferentially over all other amino acids," said Olszewski.

Further experiments showed that the parasite doesn't break down arginine in order to grow, indicating that this process serves some secondary function that helps P. falciparum proliferate within the human body. Arginine is an essential fuel for the human body's immune system, which uses it to produce a molecule called nitric oxide that is highly toxic to foreign organisms.

Researchers said the parasite-led attack on arginine could be a tool by which the parasite will "switch off" a human immune function that might threaten its survival. Now, they want to study the metabolism of P falciparum to understand how organisms adapt to a parasitic lifestyle, which is important because many of the drugs used to treat malaria successfully in the past have targeted some aspect of the parasite's metabolism.

"Designing the next generation of anti-malarial drugs will likely require a detailed knowledge of the 'weak points' in the parasite's metabolic network," said Llinas.