Ornithine decarboxylase putrescine synthesis

Figure 33. Synthesis of alkaloids from ornithine. Aikaioids are derived via putrescine or glutamic semialdehyde. At least two enzymes, ODL (Ornithine decarboxylase) or PDL (Pyrroline...

Like helminths, some protozoans also require polyamines for their cell growth, membrane stabilization and as cofactors for macromolecular synthesis. Trypanosomes have been found to possess putrescine and spermidine, but not spermine. The precursor of the polyamine biosynthesis in protozoans is ornithine, which is de-carboxylated in the presence of ornithine decarboxylase to form putrescine. Other polyamines are formed from putrescine as discussed in chapter 2 (Sec. 5.3). 

Synthesis of polyamines in the majority of cells is initiated by ornithine decarboxylase (ODC EC 4.1.1.17), which catalyses the conversion of ornithine to putrescine (Fig. 7.1) (4,13). In mammalian cells ODC undergoes rapid induction and has a short half-life. In the parasitic protozoa so far examined (T. b. brucei, P. falciparum, L. donovani and T. vaginalis), ODC has a long half-life as judged from the rate of decay of activity in the presence of cycloheximide (14-17). In African trypanosomes the slow turnover of ODC appears to be attributable to the absence of a 36 amino acid region (PEST sequence) on the COOH-terminal end (18,19). In mammalian cells, this is... 

Metcalf et al. (23) reported the synthesis of efiornithine (difluoromethyl ornithine [DFMO]) in 1978. Their interest arose from the desire to prepare ornithine decarboxylase (ODC) inhibitors as tools for studying the role of polyamines as regulators of growth processes. Ornithine decarboxylase catalyzes the conversion of ornithine to putrescine (1,4-diaminobutane), which in turn leads to the formation of the polyamines, spermine, and spermidine. It was not until 1980 that Bacchi et al. (24) demonstrated the potential of DFMO in the treatment of trypanosomiasis. 

Ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) are the first enzymes involved in the formation of tropane alkaloids (TPAs) snch as atropine and cocaine (Fig. 3). Decarboxylation of ornithine yields pntrescine, whereas arginine is converted to agmatine, which is metabolized to putrescine via a second rente. ADC is assnmed to play the primary role in TPA synthesis [18]. 

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