title: The NAD+ metabolism of Leishmania, notably the enzyme nicotinamidase involved in NAD+ salvage, offers prospects for development of anti-parasite chemotherapy.
abstract: NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox reactions it is key in the cellular energy metabolism and as a substrate it participates in many reactions leading to a variety of covalent modifications of enzymes with major roles in regulation of expression and metabolism. Cells may have the ability to produce this metabolite either via alternative de novo synthesis pathways and/or by different salvage pathways. In this issue of Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania species can only rely on the salvage of NAD+ building blocks. One of the enzymes involved, nicotinamidase, is absent from human cells. The enzyme is important for growth of Leishmania infantum and essential for establishing an infection. The crystal structure of the parasite protein has been solved and shows prospects for design of inhibitors to be used as leads for development of new drugs. Indeed, NAD+ metabolism is currently being considered as a promising drug target in various diseases and the vulnerability of Leishmania for interference of this metabolism has been proved in previous work by the same group, by showing that administration of NAD+ precursors has detrimental effect on the pathogenic, amastigote stage of this parasite.
authors.affiliation: Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium. paul.michels@uclouvain.be
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Michels
authors.forename: Luisana
authors.initials: L
authors.lastname: Avilán
mesh_terms: D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development* / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology*; D009243:NAD / Q000096:biosynthesis*; D009535:Nicotinamidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D009243:NAD; D009535:Nicotinamidase