RESUMO
Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based on drugs which are currently facing an emergence of drug resistance and in this sense the search for new drug targets is indispensable. It is well established that vitamin biosynthetic pathways, such as the vitamin B6 de novo synthesis present in Plasmodium, are excellent drug targets. The active form of vitamin B6, pyridoxal 5-phosphate, is, besides its antioxidative properties, a cofactor for a variety of essential enzymes present in the malaria parasite which includes the ornithine decarboxylase (ODC, synthesis of polyamines), the aspartate aminotransferase (AspAT, involved in the protein biosynthesis), and the serine hydroxymethyltransferase (SHMT, a key enzyme within the folate metabolism).
Assuntos
Aspartato Aminotransferases/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Malária/enzimologia , Ornitina Descarboxilase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/genética , Glicina Hidroximetiltransferase/genética , Humanos , Malária/genética , Malária/parasitologia , Ornitina Descarboxilase/genética , Plasmodium falciparum/enzimologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Vitamina B 6/metabolismoRESUMO
Malaria is an infectious disease that results in serious health problems in the countries in which it is endemic. Annually this parasitic disease leads to more than half a million deaths; most of these are children in Africa. An effective vaccine is not available, and the treatment of the disease is solely dependent on chemotherapy. However, drug resistance is spreading, and the identification of new drug targets as well as the development of new antimalarials is urgently required. Attention has been drawn to a variety of essential plasmodial proteins, which are targeted to intra- or extracellular destinations, such as the digestive vacuole, the apicoplast, or into the host cell. Interfering with the action or the transport of these proteins will impede proliferation of the parasite. In this mini review, we will shed light on the present discovery of chemotherapeutics and potential drug targets involved in protein trafficking processes in the malaria parasite.