title: Regulation and function of polyamines in African trypanosomes.
abstract: The polyamine biosynthetic pathway is an important drug target for the treatment of human African trypanosomiasis (HAT), raising interest in understanding polyamine function and their mechanism of regulation. Polyamine levels are tightly controlled in mammalian cells, but similar regulatory mechanisms appear absent in trypanosomes. Instead trypanosomatid S-adenosylmethionine decarboxylase (AdoMetDC), which catalyzes a key step in the biosynthesis of the polyamine spermidine, is activated by dimerization with an inducible protein termed prozyme. Prozyme is an inactive paralog of the active AdoMetDC enzyme that evolved by gene duplication and is found only in the trypanosomatids. In Trypanosoma brucei, AdoMetDC activity appears to be controlled by regulation of prozyme protein levels, potentially at the translational level.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Willert
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Phillips
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D053898:Biosynthetic Pathways / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D014353:Trypanosomiasis, African / Q000188:drug therapy
chemical_list: D011073:Polyamines; D014344:Trypanocidal Agents; D012437:Adenosylmethionine Decarboxylase