DefinePK

Abstract

The polyamines (putrescine, spermidine and spermine) are a group of small basic molecules distributed universally in all the living organisms including animals, plants and viruses1. Two polya­mine derivatives, putreanine and spermic acid, probably metabolites of sperniidine and spermine respectively, have also been isolated from nam­malian nervous system. 2 It was not until 1968 that the enzymology of polyamines in nammalian tissues began to be un­revealed. The enzymes needed for the synthesis of polyamines are: (1) Ornithine decarboxylase -catalysing the decarboxylation of L-ornithine to yield putrescine (2) S-adenosyl methionine decar­boxylase - forming decarboxylated adenosyhne­thionine from adenosylmethionine. (3)Spermidine synthetase - which transfers the polymine group from decarboxylated adenosylmethionine to put­rescine to yield spernildine, methyl thioa-deno­sines are formed as other reaction products. (4) spermine synthetase - catalyses the formation of spermine; the reaction is analogous to that of sper­midine synthetase (Figure -1).Relatively little is known about the catabolism and excretion of pol­yamines in animals tissues. It has been reported that about 40% of polyamines in the rat which are eliminated, are excreted in the urine as or acetylated derivatives and about 60% are catabolised by the oxidases. 3 The enzymes involved in the specific biosyn­thetic steps of polyamine production have been purified and characterised from a variety of animal sources. All of these appear to be soluble cytosol enzymes and their general properties are relatively well- documented. Ornithine decarboxylase (ODC) provides the biosynthetic route giving rise to putrescine in a reaction that maybe rate-limiting for polyamine synthesis. Polyamines and ODC ac­tivity is normally very low in quiscent tissues, but is significantly higher in rapidly proliferating cells. A large number of stimuli4 cause a rapid increase (100 to 200 fold) in the level of ODC activity, both in vivo and in cultured mammalian cells. Some of the most effective stimuli are malignant growth, high amino- acid intake, embryonic development, renal hypertrophy, cardiac enlargement, liver regeneration after hepatectomy, virus infection, thiocetamide administration, epidermal growth factor, exposure to cold and other stresses and administration of various hormones. The exact mechanism of control of ODC is not fully known but results from various studies5 suggest that in­duction of ODC in many tissues involves cyclic AMP and guanine nucleotides and its inhibition, the antizyme.