Spermine biosynthesis

Fig. 28.10. Spermidine and spermine biosynthesis (Slocum et al, 1984 used with permission of the copyright owner, Academic Press, Orlando, FL).

Adenosylmethionine, the principal source of methyl groups in the body, also contributes its carbon skeleton for the biosynthesis of the 3-diaminopropane portions of the polyamines spermine and spermidine (Figure 31-4). 

Adenosylmethionine, the methyl group donor for many biosynthetic processes, also participates direcdy in spermine and spermidine biosynthesis. 

Polyamine oxidase (amine oxygen oxidoreductase, deaminating, flavin-containing), is also a FAD-dependent enzyme and has many similarities to MAO. It is responsible for the oxidation of the secondary amino group in such substrates as A/-acetyl spermine and spermidine in the biosynthesis of spermidine and putrescine [1,12], This enzyme will not be covered in this chapter. 

Scheme 1.5.8. Spermine alkaloids and their proposed [105] biosynthesis via Michael addition.

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). 

Pantothenate (also designated vitamin B5, 64, Fig. 7) is biosynthesized de novo in plants and many microorganisms but must be obtained from nutritional sources by animals (20, 34). The branched carboxylic acid 63 is obtained from a-ketoisovalerate (61), which is an intermediate of valine biosynthesis, via 62. P-Alanine (60) is obtained by decarboxylation of aspartate (54) in microorganisms. Plants and yeasts can biosynthesize P-alanine from spermine (58) (35). An additional pathway to 60 starting from uracil (59) has been reported in plants,where... 

Figure 7 Biosynthesis of pantothenate. 54, aspartate 58, spermine 59, uracil 60, pantothenate 65, pantetheine 4-phosphate 66, coenzyme A.

Putrescine is an important intermediate in the biosynthesis of tropane alkaloids acting also as a precursor for polyamines, spermine and spermidine, and also for the biosynthesis of nicotine [111, 122]. 

The production of berberine in cell suspension cultures of T. minus var. hypoleucum was greatly enhanced via the administration of spermidine. However, the utilization of other polyamines including cadaverine, putrescine, and spermine were not effective. Experimental results indicate that spermidine induces an increase in the production of ethylene, the latter of which is definitively associated with the biosynthesis of berberine [161]. 

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). 

Like helminths, some protozoans also require polyamines for their cell growth, membrane stabilization and as cofactors for macromolecular synthesis. Trypanosomes have been found to possess putrescine and spermidine, but not spermine. The precursor of the polyamine biosynthesis in protozoans is ornithine, which is de-carboxylated in the presence of ornithine decarboxylase to form putrescine. Other polyamines are formed from putrescine as discussed in chapter 2 (Sec. 5.3). 

FIGURE 22-30 Biosynthesis of spermidine and spermine. The PLP-dependent decarboxylation steps are shaded in pink. In these reactions, 5-adenosylmethionine (in its decarboxylated form) acts as a source of propylamino groups (shaded blue). 

The polyamines spermine, spermidine, and putrescine are endogenous regulators of proliferation, differentation, functional activation, and macro-molecular biosynthesis in all mammalian cells (Selmeci et al., 1985 Morgan,... 

Rl. Raina, A., and Hannonen, P., Biosynthesis of spermidine and spermine in regenerating rat liver Some properties of the enzyme systems involved. Acta Chem. Scand. 24, 3061 (1970). 

Ci5H22NftOsS, Mr 398.44, an important methyl group donor in metabolism, e.g., in the biosynthesis of methoxybenzene derivatives and methyl esters, as well as the propylamine units of spermidine and spermine. SAM is transformed to 5-Adenosylhomocysteine in the process. The biosynthesis starts from homocysteine by transfer of the methyl groups from IV -methyltetrahy-drofolate. 

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