Vitamin B6-dependent enzymes in the human malaria parasite Plasmodium falciparum: a druggable target?

Biomed Res Int. 2014:2014:108516. doi: 10.1155/2014/108516. Epub 2014 Jan 9.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Aspartate Aminotransferases / genetics
  • Aspartate Aminotransferases / metabolism*
  • Glycine Hydroxymethyltransferase / genetics
  • Glycine Hydroxymethyltransferase / metabolism*
  • Humans
  • Malaria / enzymology*
  • Malaria / genetics
  • Malaria / parasitology
  • Ornithine Decarboxylase / genetics
  • Ornithine Decarboxylase / metabolism*
  • Plasmodium falciparum / enzymology
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / pathogenicity
  • Vitamin B 6 / metabolism

Substances

  • Antioxidants
  • Vitamin B 6
  • Glycine Hydroxymethyltransferase
  • Aspartate Aminotransferases
  • Ornithine Decarboxylase