CATIONIC PORPHYRIN DERIVATIVES AS INHIBITORS OF POLYAMINE CATABOLISM

The effects of six cationic porphyrins on several enzymes involved in polyamine biosynthesis and catabolism have been examined. Both spermid ine and spermine synthase were unaffected by the porphyrins at up to 2 mM. By contrast, ornithine and S-adenosylmethionine decarboxylase wer e inhibited by the nickel and cobalt derivatives of meso-tetrakis(N-me thyl-4-pyridiniumyl)po (T4MPyP) with re,, values in the 10-100 mu M re gion. Spermidine/spermine N'-acetyltransferase (SSAT) and polyamine ox idase (PAO) were highly sensitive to the six meso-substituted cationic porphyrins tested, with K-i values as low as 6 nM for SSAT and 85 nM for PAO. These inhibitors may prove useful in defining the structural features of the active site of these enzymes.