Polyamines are ubiquitous organic cations of low molecular weight. The content of these amines is closely regulated by the cell according to the state of growth. The reactions responsible for the biosynthesis and interconversion of the polyamines and their precursor putrescine are described and the means by which polyamine content can be varied in response to exogenous stimuli are discussed. The role of polyamines in the cell cycle, cell division, tissue growth, and differentiation is considered. Recent studies using highly specific inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithine to prevent accumulation of polyamines have indicated that the synthesis of polyamines is intimately associated with these processes. Such inhibitors have great potential for investigation of the cellular role of polyamines.

https://www.physiology.org/doi/pdf/10.1152/ajpcell.1982.243.5.C212

Polyamine metabolism and function.

Polyamines in rapid growth and cancer

The rapid involution of the rat ventral prostate after castration is an active process initiated by removal of the inhibitory effects of androgen on prostatic cell death. The present studies demonstrate that after castration-induced androgen deprivation a series of temporally discrete biochemical events are activated which result in the rapid programmed death of the subset of androgen-dependent cells within the rat ventral prostate. These biochemical steps involve 1) rapid loss of nuclear androgen receptor retention; by 12 h after castration, androgen receptors are no longer detectable in ventral prostatic nuclei; 2) an initial fragmentation of nuclear DNA into low mol wt (less than 1000 basepairs) nucleosomal oligomers which lack intranucleosomal break points; and 3) eventual complete digestion of these nucleosomal oligomers into component nucleotides. Additional studies demonstrate that activation of a Ca2+-Mg2+-dependent endonuclease is associated with this DNA fragmentation. By 4 days after castration, maximal DNA fragmentation is obtained, with 15% of the total nuclear DNA extractable as low mol wt fragments. Proteolytic enzymes are apparently not involved initially in this process, suggesting that DNA fragmentation is a discrete event in, rather than a result of, cell death. Flow cytometric analysis of nuclear DNA content demonstrated that each day after castration, a subpopulation of androgen-dependent cells in rat ventral prostate fragmented all of their genomic DNA, as opposed to the whole population of cells fragmenting an increasing portion of their DNA daily.

Activation of programmed cell death in the rat ventral prostate after castration.

Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors.

A single topical application of 10 mg of crotol oil or 17 nmoles of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) resulted in a rapid, transient stimulation of mouse epidermal ornithine decarboxylase activity The activity reached a peak (230-fold greater than control after TPA) at 4 to 5 hr after croton oil or TPA treatment and returned to control level by 12 hr The stimulation of S-adenosyl-L-methionine decarboxylase activity was less pronounced, reaching a peak of activity (6- to 7-fold greater than control) at 9 to 12 hr after TPA or croton oil and slowly declining to control level The stimulation of both enzyme activities was dependent on the dose of TPA applied and correlated well with the promoting ability of these doses on mouse skin Phorbol, the nonpromoting parent alcohol of TPA, did not affect the enzymes activities Cycloheximide pretreatment abolished the increase in enzyme activities after TPA application By measuring the decline of enzyme activity following cycloheximide treatment, enzyme half-lives of 17 and 41 min were obtained for ornithine and S-adenosyl-L-methionine decarboxylase, respectively 5-Azacytidine pretreatment prevented the stimulation of enzyme activities by TPA, while actinomycin D had no effect Cordycepin (3'-deoxyadenosine) partially blocked the rise in enzyme activities

Induction of the Polyamine-biosynthetic Enzymes in Mouse Epidermis by Tumor-promoting Agents

On the Role of S-Adenosyl-l-methionine in the Biosynthesis of Spermidine by Rat Prostate

In the rat ventral prostate gland the biosynthesis of putrescine, a precursor of spermidine and spermine, is shown to occur by the direct decarboxylation of l-ornithine. Some properties of a soluble pyridoxal phosphate-dependent l-ornithine decarboxylase are described. The findings are discussed in relation to other enzymic reactions involved in the biosynthesis of polyamines by the prostate gland.

/pdf/biosynthesis-of-putrescine-in-the-prostate-gland-of-the-rat-39x7a4na8a.pdf

Biosynthesis of putrescine in the prostate gland of the rat.

1 Castration of adult rats resulted in marked decreases in the amounts of putrescine, spermidine and spermine in the ventral prostate gland Spermidine concentrations decline rapidly over the first 11 days after androgen withdrawal, reaching a value of only 12% of normal controls Spermine concentrations diminish more slowly, reaching 24% of normal within 11 days The spermidine/spermine molar ratio falls from 09 to 046 under these conditions Putrescine concentrations decrease by 70% at 7 days after castration and then remain constant for some days 2 After daily injections of testosterone propionate to rats castrated 7 days previously, prostatic spermidine and putrescine concentrations increase significantly within 24h; normal or even greater values are observed within 8 and 4 days respectively In contrast, the spermine concentration does not increase until 5 days after commencement of androgen treatment 3 The activities of two enzymes involved in polyamine biosynthesis (ornithine decarboxylase and a putrescine-activated S-adenosyl-l-methionine decarboxylase system) were greatly decreased soon after castration: after 7 days the respective values were 15% of normal for ornithine decarboxylase and 7% of normal for putrescine-dependent decarboxylation of S-adenosyl-l-methionine Injection of testosterone propionate into animals castrated 7 days previously induced a rapid increase in both enzymic activities: ornithine decarboxylase was doubled in 6h, and increased three- to four-fold within 48h, whereas the putrescine-dependent decarboxylation of S-adenosyl-l-methionine doubled in 3h and increased tenfold within 48h of commencement of daily androgen treatments 4 The activity of these enzyme systems was very low in the ventral prostates of hypophysectomized rats and was increased by administration of testosterone in a manner similar to that found in castrated rats 5 Alterations in the activity of two ventral-prostate enzymes involved in ornithine production (arginase) and utilization (ornithine-2-oxoglutarate transaminase) that result from changes in the androgenic status of rats are described 6 The findings presented suggest that the activities of ornithine decarboxylase and the putrescine-dependent S-adenosyl-l-methionine decarboxylase system, rather than ornithine concentrations, are rate-limiting for the formation of putrescine and polyamines in rat ventral prostate 7 The relation of polyamines to androgen-induced prostatic growth is discussed with particular reference to the biosynthesis of proteins and nucleic acids

/pdf/concentrations-of-putrescine-and-polyamines-and-their-16xxn4c2gt.pdf

Concentrations of putrescine and polyamines and their enzymic synthesis during androgen-induced prostatic growth.

Polymerization of deoxyribonucleotides in relation to androgen-induced prostatic growth☆

A soluble enzyme preparation catalysing the release of adenine from 5′-methylthioadenosine was purified some 30-fold from extracts of the rat ventral prostate This reaction was completely dependent on addition of inorganic phosphate ions to the assay medium This absolute requirement for phosphate ions suggests a phosphorolytic cleavage mechanism After acid treatment, the other product of the reaction appeared to be 5-methylthioribose The actions of some other well-characterized enzymes of nucleoside metabolism of 5′-methylthioadenosine were also investigated; purified purine nucleoside phosphorylases from calf spleen and human erythrocytes did not attack 5′-methylthioadenosine The role of 5′-methylthioadenosine in mammalian tissues is discussed

/pdf/phosphate-stimulated-breakdown-of-5-methylthioadenosine-by-3uw7sqm88j.pdf

H. G. Williams-Ashman

Papers

On the Role of S-Adenosyl-l-methionine in the Biosynthesis of Spermidine by Rat Prostate

Biosynthesis of putrescine in the prostate gland of the rat.

Concentrations of putrescine and polyamines and their enzymic synthesis during androgen-induced prostatic growth.

Polymerization of deoxyribonucleotides in relation to androgen-induced prostatic growth☆

Phosphate-stimulated breakdown of 5'-methylthioadenosine by rat ventral prostate.