Physiological aspects of ornithine decarboxylaseOrnithine decarboxylase (ODC, L-ornithine carboxylyase, EC 4.1.1.17) is the rate limiting enzyme in the biosynthesis of polyamines. Its occurrence in animal tissue was reported independently by three laboratories in 196813, and its activity increases in various growing tissues and organs. During recent years, this enzyme, and its regulation, have attracted considerable attention and available information has been summarized in several reviewsk7. It is now well established that virtually all hormones cause the increase of ODC activity in appropriate target tissues (Tubte 1). In many cases, this increase is mediated by cyclic AMP ( Table 2).
Properties of ornithine decarboxylaseThe properties of ornithine decarboxylase are dealt with in the previous Paper by A. M. Kaye (p 2).
Regulation of ornithine decarboxylase activityOne of the typical features of ODC is its short half-life, which ranges from 15 to 45 min. This is the shortest half-life of any enzyme in eukaryotes. To account for such rapid changes in activity, several mechanisms have been proposed6'. The three major mechanisms are depicted in Table 3.
AntizymeIn 1976, Canellakis and coworkers6' described an M, 26 000 protein, which was formed upon treating cells in culture with 5-10 mM putrescine. This protein, which was designated as antizyme, formed complexes with ODC and neutralized its activity. The complex could be dissociated by ammonium sulphate or by relatively high salt concentration of 250 m~~~. The antizyme was first detected in H-35 rat hepatoma cells, L-1210 mouse leukaemia cells, N-18 mouse neuroblastoma cells, rat liver, and subsequently, also in many other cell linesm and also in bacteria65. It is noteworthy that the antizyme appeared to be ubiquitous and a bacterial antizyme could neutralize a mammalian a n t i~y r n e~~.One difficulty in studies on antizymes has been the lack of an appropriate method for the assay of the intracellular amount of enzyme-antizyme complexes. Fujita et al. have recently described the presence of an 'antizyme inhibitor' in rat liver66. This protein, which resembles ODC in its molecular weight, could replace antizyme in a complex with ODC, and reactivate the latter. It is tempting to speculate that this antizyme inhibitor is a modified form of ODC (such as a phosphorylated or transaminated form). This assumption should be confirmed by peptide and immunological analyses. The 'antizyme inhibitor' could eventually be used for the assay of the amount of inactive ODC in a complex with antizyme". It is not certain why the polyamine-dependent protein kinase of P. polycephalum required both calcium ions and calmodulin for phosphorylation, while that of the hepatoma cells only required calmodulin. This discrepancy may be explained by the different source of the enzymes and by the degree of purity. One enzyme was of fungal origin, while the other was a mammalian one. Moreover, the P. polycephalum enzyme was derived from nuclear extract, and autophosphorylation was measured. The ...
