Isoelectric shifts in ornithine decarboxylase as a biomarker of aquatic toxicology

Ornithine decarboxylase (ODC) is the initial rate-limiting enzyme in the biosynthesis of polyamines, the organic cations of the cell. Expression of ODC is absolutely required for the growth of all cell types. Ornithine decarboxylase has the striking property among vertebrate enzymes in that under normal conditions it has a short intracellular half-life of 15-20 minutes and the level of expression is minimal. However, after exposure to a toxic or carcinogenic stimulus the amount of ODC activity in the tissue is markedly increased in parallel to the degree of toxicity, increasing from 25-1000-fold above the normal tissue. We have found that one of the molecular mechanisms which leads to this marked increase in ODC activity is an increase in the stability of the enzyme to intracellular proteolysis which is due to progressive increases in the phosphorylation state of the enzyme resulting in more acidic isoelectric forms of ODC. We have tested this phenomena as a potential biomarker of aquatic toxicity by analyzing livers of flounder from Galveston Bay which were normal versus cancerous. The activity of ODC in the cancerous flounder livers was 100-times greater than that present in the normal flounder livers. Our results suggest that analysis of the isoelectric status of ODC in livers from aquatic animals may provide a useful biomarker for the extent of aquatic toxicology. (DBO)