Catalytic irreversible inhibition of bacterial and plant arginine decarboxylase activities by novel substrate and product analogues

• Published in: Biochemical journal Vol. 242; no. 1; pp. 69 - 74
• Main Authors: Bitonti, A J, Casara, P J, McCann, P P, Bey, P
• Format: Journal Article
• Language: English
• Published: England 15-02-1987
• Subjects: Agmatine - analogs & derivatives; Agmatine - pharmacology; Arginine - analogs & derivatives; Arginine - pharmacology; Avena sativa; Carboxy-Lyases - antagonists & inhibitors; Edible Grain - drug effects; Edible Grain - enzymology; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - enzymology; Hordeum - drug effects; Hordeum - enzymology; Hordeum vulgare; Putrescine - analogs & derivatives; Putrescine - pharmacology
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2420069

Arginine decarboxylase (ADC) activity from Escherichia coli and two plant species (oats and barley) was inhibited by five new substrate (arginine) and product (agmatine) analogues. The five compounds, (E)-alpha-monofluoromethyldehydroarginine (delta-MFMA), alpha-monofluoromethylarginine (MFMA), alpha-monofluoromethylagatine (FMA), alpha-ethynylagmatine (EA) and alpha-allenylagmatine (AA), were all more potent inhibitors of ADC activity than was alpha-difluoromethylarginine (DFMA), the only irreversible inhibitor of this enzyme described previously. The inhibition caused by the five compounds was apparently enzyme-activated and irreversible, since the loss of enzyme activity followed pseudo-first-order kinetics, was time-dependent, the natural substrate of ADC (arginine) blocked the effects of the inhibitors, and the inhibition remained after chromatography of inhibited ADC on Sephadex G-25 or on overnight dialysis of the enzyme. DFMA, FMA, delta-MFMA and MFMA were effective at very low concentrations (10 nM-10 microM) at inhibiting ADC activity in growing E. coli. FMA was also shown to deplete putrescine effectively in E. coli, particularly when combined with an inhibitor of ornithine decarboxylase, alpha-monofluoromethyl-putrescine. The potential uses of the compounds for the study of the role of polyamine biosynthesis in bacteria and plants is discussed.