Polyamine metabolism regulation

Perez-Leal O, Merali S (2012) Regulation of polyamine metabolism by translational control. Amino Acids 42 611-617... 

ACS activity may be reversibly regulated by various substances associated with the methionine-recycling pathway, SAM metabolism, and polyamine synthesis, and by natural and chemical analogues of SAM or inhibitors of PLP-dependent enzymes. 

Metabolism of polyamines has a direct action on cell proliferation. Thus, it is a therapeutic target for the design of antitumor agents. However, inhibition of ornithine decarboxylase (ODC) by specific inhibitors does not completely cancel the activity. This is due to the existence of other biosynthetic pathways (i.e., SAM-DC). These pathways are themselves regulated by polyamines. 

A number of the products of the decarboxylation of amino acids shown in Table 9.2 are important as neurotransmitters and hormones, such as dopamine, noradrenaline, adrenaline, serotonin (5-hydroxytryptamine), histamine, and Y - aminobutyric acid (GABA), and as the diamines agmatine andput-rescine and the polyamines spermidine and spermine, which are involved in the regulation of DNA metabolism. The decarboxylation of phosphatidylser-ine to phosphatidylethanolamine is important in phospholipid metabolism (Section 14.2.1). 

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). 

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]. 

Kevers, C. Le Gal, N. Monteiro, M. Dommes, J. Gaspar, T. (2000). Somatic embryogenesis of Panax ginseng in liquid cultures a role polyamines and their metabolic pathways. Plant Growth Regulation, Vol. 31, No. 3, pp 209-214, ISSN 0167-6903. 

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