Spermidine biosynthesis

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

Most pyrrolizidine alkaloids are esters of basic alcohols known as necine bases. The most frequently studied pyrrolizidine alkaloids are formed from the polyamines, putrescine and spermidine, and possess one of three common necine bases retronecine, heliotridine, and otonecine. Putrescine is utilized exclusively as a substrate in secondary metabolism, whereas spermidine is a universal cell-growth factor involved in many physiological processes in eukaryotes. Spermidine biosynthesis begins with the decarboxylation of SAM by SAM decarboxylase 165). The aminopropyl group is then transferred from decarboxylated SAM to putrescine by spermidine synthase to form spermidine (Scheme 5). Putrescine can be produced from ornithine by ODC. However, putrescine is derived from the arginine-agmatine pathway in pyrrolizidine alkaloid-producing plants due to the absence of ODC activity 166). 

It is possible that the selection of aspartate p-sanialdehyde over AdoMet for spermidine biosynthesis in many bacteria is influenced by the metabolic cost of AdoMet consumption. 

Bolhnger JM Jr, Kwon DS, Huisman GW, Kolter R, Walsh CT (1995) Glutathionylspermidine metabolism in Escherichia coli. Purification, cloning, overproduction, and characterization of a bifunctional glutathionylspermidine synthetase/amidase. J Biol Chem 270 14031-14041 Bowman WH, Tabor CW, Tabor H (1973) Spermidine biosynthesis. Purification and properties of propylamine transferase from Escherichia coli. J Biol Chem 248 2480-2486 Chattopadhyay MK, Tabor CW, Tabor H (2009) Polyamines are not required for aerobic growth of Escherichia coli preparation of a strain with deletions in all of the genes for polyamine biosynthesis. JBacteriol 191 5549-5552... 

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). 

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. 

The first committed step in TA and nicotine biosynthesis is catalyzed by putrescine JV-methyltransferase (PMT) (Fig.7.4).82 A PMT cDNA isolated from tobacco showed extensive homology to spermidine synthase from mammalian and bacterial sources.83 A-Methylputrescine is oxidatively deaminated to 4-aminobutanal, which undergoes spontaneous cyclization to form the reactive A-methyl-A1-pyrrolinium cation. Although the enzymes involved are unknown, the A-methyl-A1-pyrrolinium cation is thought to condense either with acetoacetic acid to yield hygrine as a precursor to the tropane ring, or with nicotinic acid to form nicotine. 

Figure 9.2. Metabolism of pyrrolizidine alkaloids (PAs) in Senecio vernalis. The substrates for alkaloid biosynthesis, putrescine and spermidine, are derived from primary metabolism. Homospermidine, synthesized by homospermidine synthase (HSS), is the first pathway specific intermediate. It is exclusively incorporated into the necine base moiety of senecionine A-oxide, the backbone structure of all PAs found in this Senecio species. During allocation from the roots as site of synthesis to the shoots, it is chemically modified to provide the species specific PA-pattem.

BOTTCHER, F., OBER, D., HARTMANN, T., Biosynthesis of pyrrolizidine alkaloids Putrescine and spermidine are essentail substrates of enzymatic homospermidine formatioa Can. J. Chem., 1994,72, 80-85. 

Figure 2.4 Biosynthesis of the pyrrolizidine alkaloid. senecionine-N-oxide. ODC, ornithine decarboxylase ADC, arginine decarboxylase SPDS, spermidine synthase HHS, homospermidine synthase. (See Plate 9 in colour plate section.)...

Bottcher, F, Ober, D. and Hartmann, T. (1994) Biosynthesis of pyrrolizidine alkaloids putrescine and spermidine are essential substrates of enzymatic homospermidine formation. Can. ]. Chem., 72, 80-5. 

Graser, G. and Hartmann, T. (2000) Biosynthesis of spermidine, a direct precursor of pyrrolizidine alkaloids in root cultures of Senecio vulgaris L. Planta, 211,239-45. 

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). 

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