Sorais Françoise, Niño-Vega Gustavo, San-Blas Gioconda
Instituto Venezolano de Investigaciones Científicas, Centro de Microbiología y Biología Celular, Caracas, Venezuela.
Rev Iberoam Micol. 2003 Mar;20(1):1-5.
Ornithine decarboxylase (ODC) is the first enzyme in polyamine biosynthesis in numerous living organisms, from bacteria to mammalian cells. Its control is under negative feedback regulation by the end products of the pathway. In dimorphic fungi, ODC activity and therefore polyamine concentrations are related to the morphogenetic process. From the fission yeast Schizosaccharomyces pombe to human, polyamines induce antizyme synthesis which in turn inactivates ODC. This is hydrolyzed by the 26S proteasome without ubiquitination. The regulatory mechanism of antizyme on polyamines is conserved, although to date no antizyme homology has been identified in some fungal species. The components that are responsible for regulating polyamine levels in cells and the current knowledge of ODC regulation in dimorphic fungi are presented in this review. ODC degradation is of particular interest because inhibitors of this pathway may lead to the discovery of novel antifungal drugs.
鸟氨酸脱羧酶(ODC)是从细菌到哺乳动物细胞等众多生物体中多胺生物合成的第一种酶。其调控受该途径终产物的负反馈调节。在双态真菌中,ODC活性以及多胺浓度与形态发生过程相关。从裂殖酵母粟酒裂殖酵母到人类,多胺诱导抗酶合成,而抗酶反过来使ODC失活。这是由26S蛋白酶体水解的,无需泛素化。尽管迄今为止在一些真菌物种中尚未鉴定出抗酶同源物,但抗酶对多胺的调控机制是保守的。本文综述了负责调节细胞内多胺水平的成分以及双态真菌中ODC调控的现有知识。ODC降解特别令人感兴趣,因为该途径的抑制剂可能会导致发现新型抗真菌药物。