Control of Ornithine Decarboxylase Activity in Physarum by Polyamines

Abstract

The addition of putrescine, spermidine, or spermine, to cultures of Physarum p~I y c e~h a / u m rapidly reduced the activity of ornithine decarboxylase, with maximal inhibition, 80 -90 %, occurring after 90 min. This response was not due to a decrease in enzyme molecules, but rather to the rapid conversion of the active enzyme to a stable, catalytically less active form. This response to exogenous polyamines was not accompanied by the appearance of a macromolecular inhibitor (antizyme) either free, or bound to the enzyme. Physiological levels of the polyamines were also found to inhibit this enzyme in vitro both competitively and non-competitively, and to promote complete yet reversible inactivation of this enzyme in the absence of reducing agents. The data suggest that the control of this enzyme by endogenous polyamine levels may be distinct from its response to exogenous polyamines.

Equilibrium between active and inactive forms of rat liver ornithine decarboxylase mediated by L‐ornithine and salts

“…Several modified forms of the enzyme have been reported, including phosphorylated [7] and transamidated forms [6], and the existence of an equilibrium between active and cryptic forms of ODC has also been suggested [lo]. Moreover, different investigators have observed multiple &forms of ODC after fractionation by gel permeation chromatography [13,17], but the physiological significance of these forms remains unknown.…”

Osmotically‐induced modification of ornithine decarboxylase in Physarum

“…The data presented here, as well as past studies on Physarum [8] and mammalian cells [ 1,2,11] correlating cell membrane integrity with intracellular ODC activity, suggest that the mechanism interconverting ODC forms may be located at the cell membrane. Furthermore, the inhibition of this osmoticallyinduced activation, but not inactivation, by sodium azide suggests that only the former reaction may be ATP dependent.…”

“…In E co&, for example, osmotic shock induces the loss of most cellular putrescine, and uptake of K' from the media, within 5 min [7]. A similar release of cellular polyamines to the media might be sufficient to induce inactivation of ODC in Physarum [8], yet this is not likely as the response time to extracellular polyamines has been shown to be considerably longer than the 4-6 min required for the osmotic effect. Furthermore the reabsorption of the released polyamine would not be fast enough to produce the observed rapid return to initial enzyme activity levels.…”

“…Furthermore the reabsorption of the released polyamine would not be fast enough to produce the observed rapid return to initial enzyme activity levels. It is more likely that exogenous polyamines [8] and osmotic shock, as well as the presence of inhibitors [9] and variations in growth and development [4,10], are all separate factors capable of influencing the common mechanism responsible for posttranslational activation and inactivation of ODC.…”

Polyamines and cellular adenosine 3′ :5′-cyclic monophosphate

“…A substantial increase in the intracellular polyamines is observed when extracellular concentrations rise to the endogenous concentrations (Clark & Fuller, 1975;Heller et al, 1978) and furthermore exogenous polyamines appear not to enter the same pool as amines synthesized within the cell (Russell et al, 1970). These findings, together with the observed sensitivity of most cells to exogenous polyamine in the presence of much higher endogenous concentrations (Mitchell et al, 1978;Heller et al, 1978), make it difficult at present to assess the reason for different effects on cyclic AMP of increasing concentrations ofexogenous polyamines. We are tempted to suggest that this phenomenon might be related to a different availability of free and more active polycations inside the cell.…”