Polyamines synthesis, regulation

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. 

AdoMet is a critical branch point metabolite. In its decarboxylated form, it serves as aminopropyl group donor in polyamine synthesis as AdoMet it is the methyl group donor for most transmethylation reactions (Fig. 7.1). In eukaryotic cells AdoMet decarboxylase is activated by putrescine and is the rate-limiting step of polyamine biosynthesis. Since production of dc-AdoMet is irreversible (13) regulation of AdoMet decarboxylase by putrescine determines the overall rate of polyamine synthesis. 

The IGF-I-independent actions of GH are exerted primarily in hepatocytes. GH administration is followed by an early increase in the synthesis of 8 to 10 proteins, among which are IGF-I, a2-macroglobulin, and the serine protease inhibitors Spi 2.1 and Spi 2.3. Expression of the gene for ornithine decarboxylase, an enzyme active in polyamine synthesis (and, therefore, in the regulation of cell proliferation), is also significantly increased by GH. 

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. 

In contrast to the harmful biogenic amines, the polyamines putrescene, spermidine and spermine are necessary for optimal growth and function of cells. They are involved in DNA, RNA and protein synthesis, regulation of gene expression, enzyme activity, cell proliferation and cell signaUtng. 

A correlation of enhanced synthesis of polyamines with rapid growth or cell proliferation has been observed 21. From a physiological point of view, polyamines are implicated as regulators of cell proliferative activity 22). It is well known that polyamines, as protonated polycations, can bind with nucleotide and nucleic acid anions 23 241 to affect biochemical reactivities and stabilize tertiary structures 25,26). 

Tire synthesis of polyamines is tightly regulated. The PLP-dependent ornithine decarboxylase is present in very low concentrations226 and apparently has the shortest half-life ( 10 min) of any mammalian... 

Palanimurugan R, Scheel H, Hofmann K, Dohmen RJ (2004) Polyamines regulate their synthesis by inducing expression and blocking degradation of ODC antizyme. EMBO J 23 4857 1867... 

As mentioned earlier, there are at least 50 putative transmitters that could potentially play a role in synaptic transmission or in neurochemical processes. These include acetylcholine, the aromatic monoamines (catecholamines and indole amines), a variety of primary and polyamines, certain amino acids, certain purine nucleosides and nucleotides, and a large number of peptides. The biosynthesis and regulation of the turnover of these putative transmitters will be discussed in another section of this article. However, it is worth noting here that the synthesis of these sundry transmitters is complex and variable, and in most cases the biologic control of the synthesis and degradation of these compounds is poorly understood at best. 

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