A schematic overview of the Spd-mediated hypusination process of eIF5A in plants and related pathways. Spd is essential for the DHS reaction to produce deoxyhypusine (Dh-Hyp) on inactive forms of eIF5A via cofactor NAD+. Spd is derived from both the PA biosynthesis catalysed by Spd-synthase (SPDS) and catabolism by polyamine oxidases (PAOs). It is worth mentioning that the metabolism of Spd is strongly connected to the biosynthesis of important signal molecules such as nitric oxide (NO), hydrogen peroxide (H2O2), gamma-aminobutyric acid (GABA), and ethylene (ET) providing routes for the complex influence of Spd levels in plants. The second step of hypusination is catalysed by DOHH, which needs oxygen and diiron for its function, in order to produce the hypusine of mature eIF5A. Abbreviations: Put—putrescine; Spm—spermine; L-Arg—L-arginine; L-Orn—L-ornithine; ADC—arginine decarboxylase; ODC—ornithine decarboxylase; CuAO—copper amine oxidase; SPMS—spermine synthase; T-SPMS—thermospermine synthase.