Activation of rat brain ornithine decarboxylase by GTP

Abstract

The activity of ornithine decarboxylase (ODC) measured in different regions of rat brain was highest in the hippocampus and lowest in the cerebellum. The ODC activity of a crude extract of the cerebellum was increased by the addition of GTP to the enzyme assay. Following dissociation of the ODC-antizyme complex by Sephadex G-75 chromatography in buffer containing 0.25 M NaCl, the GTP-activatable ODC was found in every brain region analysed. This GTP-activatable brain ODC has greater affinity for antizyme than the non-GTP-activatable brain ODC or the kidney ODC. The irreversible inhibitor of ODC, alpha-difluoromethylornithine (DFMO), inhibited approx. 60% of the ODC activity of all brain regions, whereas kidney ODC was inhibited totally by DFMO. When extracts of brain and kidney were incubated at 55 degrees C, kidney ODC was rapidly inactivated, but brain ODC was more heat-stable. Brain ODC, but not kidney ODC, was activated by GTP and ATP, and also by their deoxy forms. The K1/2 for activation of the enzyme was 2 microM for GTP and 40 microM for ATP. Using partially purified brain ODC, the activation by GTP was irreversible. These results demonstrate for the first time that the GTP-activatable ODC exists in the brain and is associated with the antizyme. The possible mechanisms of activation by GTP, the significance of this finding for the regulation of brain ODC, and the similarities to and differences from the GTP-activatable ODC found in certain rodent and human tumours are all discussed.

Ornithine decarboxylase activity during the development of Anastrepha fraterculus (Diptera, Tephritidae)

“…This ability to activate brain ODC was stronger in cerebellum enzymes and weaker in hippocampus ODC. The K m value is affected by GTP and the value of V max also changes in every brain region (Kilpelainen and Heitala, 1994). These results suggest that the GTP effect on ODC activity is tissue-specific.…”

Expression of a Novel Human Ornithine Decarboxylase-like Protein in the Central Nervous System and Testes

“…There is a general discrepancy between the relatively high amounts of ODC protein in the central nervous system (CNS) and its low or modest catalytic activity (10). Kilpelä inen and Hietala (11) found that in the adult rat brain, ODC could be activated by GTP and that the activity was partially resistant to treatment with the ODC inhibitor, ␣-difluoromethyl ornithine (DFMO). They suggested the existence of an alternative isoform of ODC in the brain.…”

Rapid and regulated degradation of ornithine decarboxylase

“…The only possible allosteric regulator of ODC known is GTP, which activates ODC of Escherichia coli, some tumour cells [11,12] and rat brain [13]. Changes in ODC activity are in general associated with parallel changes in the amount present, except at very low enzyme levels where a significant fraction of ODC may be present as an inactive complex with antizyme [14,15].…”