Polyamine metabolism biosynthesis

Polyamines regulate a number of biochemical functions in mammals as well in the parasites. The presence of these amines has been demonstrated in some helminths. Others, such as the buffalo filarial worm, Setaria cervi, which lack the enzymes essential for the biosynthesis of polyamines, depend on their host to meet the requirement of these amines [65a]. Consequently, the inhibition of the uptake of polyamines, their biosynthesis or metabolic functions also provide useful targets for design of potential anthelmintics [65a,b]. 

Polyamine metabolism by parasites differs in several significant ways from the mammalian host these include, but are not limited to, enzyme half-life, turnover, substrate specificity, types and quantities of polyamines produced. The production of the novel bis glutathionyl spermidine adduct by trypanosomatids, its role as an antioxidant and the protein structure of trypanothione reductase is discussed with respect to the more conventional glutathione reductase system. The role of S-adenosylmethionine and decarboxylated S-adenosylmethionine as critical precursors in the biosynthesis of the higher polyamines is explored with respect to differences in the function and control of the pathway by various parasites. Polyamine biosynthesis in parasites is sufficiently different from that of the host to afford multiple opportunities for drug development, these may be aimed directly at circumventing polyamine biosynthesis or at inhibiting precursors necessary for polyamine synthesis. 

Slocum, R. D. and A. W. Galston, Inhibition of polyamine biosynthesis in plants and plant pathogenic fungi, in Inhibition of Polyamine Metabolism (P. P. McCann et al., eds.), 305-316, Academic Press, New York, 1987. 

Tun NN, Santa-Catarina C, Begum T et al (2006) Polyamines induce rapid biosynthesis of nitric oxide (NO) in Arabidopsis thaliana seedlings. Plant Cell Physiol 47 346-354 Vujcic S, Diegelman P, Bacchi CJ et al (2002) Identification and characterization of a novel flavin-containing spennine oxidase of mammalian cell origin. Biochem J 367 665-675 Wallace HM, Fraser AV, Hughes A (2003) A perspective of polyamine metabolism. Biochem 1 376 1-14... 

Central Intermediary Metabolism Amino sugars Phosphorus compounds Polyamine biosynthesis Sulfur metabolism Nitrogen fixation Other... 

One reaction of arginine metabolism also apparently takes place in the hydrogenosomes. Arginine is a precursor in the biosynthesis of polyamines, the... 

Precursors of /1-alanine 3 biosynthesis are uracil 2, L-aspartate 4, and polyamines which are subjected to degradation in distinct ways - whereas uracil is metabolized by hydrogenation followed by hydrolysis, polyamines like spermine 1 are oxidized and L-aspartate is decarboxylated (Scheme 1.6.1). 

HARTMANN, T SANDER, H., ADOLPH, R.D., TOPPEL, G., Metabolic links between the biosynthesis of pyrrolizidine alkaloids and polyamines in root cultures of Senecio vulgaris. Planta, 1988,175,82-90. 

Nitrogen Metabolism "" " i i (ammonia incorporation, amino acid biosynthesis, nitrate/nitrite reduction, proline oxidation, polyamine biosynthesis)... 

Polyamine biosynthesis is associated with regulation of a number of metabolic functions including growth of cells in most of the living organisms. In mammals, ornithine is the precursor of aliphatic polyamines. Putrescine, formed by decarboxylation of the former by ornithine decarboxylase, is the first amine formed in polyamine biosynthesis. Putrescine gives rise to the other two polyamines, spermine and spermidine by successive addition of 3-aminopropyl residues derived from S-adenosyl-L-methionine (SAM) in the presence of different enzymes [44] (Chart 7). 

Other candidates are the polyamine and jasmonic acid families, and all have precursors, metabolites, conjugates, and synthetic analogues. Their biosynthesis and metabolism, which provide additional control points for their function, are studied intensively. 

Deficiency of either vitamin Bj or folate decreases the synthesis of methionine and SAM, thereby interfering with protein biosynthesis, a number of methylation reactions, and the synthesis of polyamines. In addition, the cell responds to the deficiency by redirecting folate metabolic pathways to supply increasing amounts of methyltetrahydrofolate this tends to preserve essential methylation reactions at the expense of nucleic acid synthesis. With vitamin Bj deficiency, methylenetetrahydro-folate reductase activity increases, directing available intracellular folates into the methyltetrahydrofolate pool (not shown in Figure 53-6). The methyltetrahydrofolate then is trapped by the lack of sufficient vitamin Bj to accept and transfer methyl groups, and subsequent steps in folate metabolism... 

Most pyrrolizidine alkaloids are esters of basic alcohols known as necine bases. The most frequently studied pyrrolizidine alkaloids are formed from the polyamines, putrescine and spermidine, and possess one of three common necine bases retronecine, heliotridine, and otonecine. Putrescine is utilized exclusively as a substrate in secondary metabolism, whereas spermidine is a universal cell-growth factor involved in many physiological processes in eukaryotes. Spermidine biosynthesis begins with the decarboxylation of SAM by SAM decarboxylase 165). The aminopropyl group is then transferred from decarboxylated SAM to putrescine by spermidine synthase to form spermidine (Scheme 5). Putrescine can be produced from ornithine by ODC. However, putrescine is derived from the arginine-agmatine pathway in pyrrolizidine alkaloid-producing plants due to the absence of ODC activity 166). 

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