Arginine decarboxylase inhibitors

Bagni, N., Torrigiani, P., and Barbieri, R, In vitro and in vivo effect of ornithine and arginine decarboxylase inhibitors in plant tissue culture, Adv. Polyamine Res., 4, 409-417, 1983. 

Kierszenbaum, F., Wirth, J. J., McCann, P. P. and Sjoerdsma, A. (1987) Arginine decarboxylase inhibitors reduce the capacity of Trypanosoma cruzi to infect and multiply in mammalian host cells. Proc. Natl. Acad. Sci. USA 84 4278-4282. 

Further modifications using the same strain of ODC S. cerevisiae reconstituted a bacterial/plant polyamine synthesis pathway in yeast [41], The ODC strain was transformed with plasmids encoding arginine decarboxylase and ag-matine ureohydrolase, which conferred polyamine-independent growth on the recombinant microbe. A similar construction could be used to screen for inhibitors of the homologous enzymes from Apicomplexan protozoa, which synthesize poly amines through this pathway [42]. 

Arginine decarboxylase (ADC) catalyzed decarboxylation of arginine is the initial step in an alternative pathway to putrescine in bacteria and higher plants. a-Difluoro-methylarginine (DFMA) (110)17 is an effective mechanism-based inhibitor of ADC and has been used to study compensatory processes involving ADC and ODC175. 

The use of suicide inhibitors of ornithine decarboxylase and arginine decarboxylase, coupled with the efficiency of incorporation of labelled precursors, led to the conclusion that arginine decarboxylase was the source of putrescine for tobacco alkaloids including 1 and 2 [46], Labelled spermidine was incorporated into 1 and 2, apparently via degradation to putrescine [47]. In vitro properties of the nicotine demethylase activity from Nicotiana otophora were characterized [59]. 

Fig. 2. Biogenetic links between A primary metabolism and B the alkaloid-specific pathway. CAP, N-carbamoylputrescine GABA, 4-aminobutyric acid. Inhibitors DFMA, a-difluorome-thylarginine, HEH, /1-hydroxyethylhydrazine. Enzymes 1, arginine decarboxylase 2, agmatine iminohydrolase 3, JV-carbamoylputrescine amidohydrolase 4, diamine oxidase 5, pyrroline dehydrogenase (NAD+-dependent) 6, spermidine synthase 7, a putrescine-producing poly-amine oxidase (H H-insensitive) 8, homospermidine synthase 9, an HEH-sensitive polyamine oxidase...

Polyamines such as spermine and spermidine, involved in DNA packaging, are derived from methionine and ornithine by the pathway shown in Figure 22-30. The first step is decarboxylation of ornithine, a precursor of arginine (Fig. 22-10). Ornithine decarboxylase, a PLP-requiring enzyme, is the target of several powerful inhibitors used as pharmaceutical agents (Box 22-2). ... 

Various enzymes, lysozyme, catalase, phosphatase, malate/formate dehydrogenase, adenylase kinase, pymvate decarboxylase, alkaline phospatase, serum albumin, lipoprotein, interferon, growth factor, polypeptide hormone DNA, RNA, y-globulin, proteinase, carboxypeptidase, endotoxins, pyrogen, IgG, trypsin inhibitor, transferrin, casein, L-benzoyl arginine ethyl ester, cytocrome C IgG, heparin... 

These amides were labelled after Incubation with the Indicated precursors. a-Difluoromethylomlthlne, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, did not reduce the incorporation of ornithine into these clnnamoyl-putrescines, suggesting that the putrescine is formed via arginine. The amounts of these amides in this cell-suspension culture were increased when the concentration of phosphate in the culture medium was reduced305 ). 

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