Current status of the polyamine research field

Abstract

This chapter provides an overview of the polyamine field and introduces the 32 other chapters that make up this volume. These chapters provide a wide range of methods, advice, and background relevant to studies of the function of polyamines, the regulation of their content, their role in disease, and the therapeutic potential of drugs targeting polyamine content and function. The methodology provided in this new volume will enable laboratories already working in this area to expand their experimental techniques and facilitate the entry of additional workers into this rapidly expanding field.

Fig 1

Structures of some naturally occurring polyamines. It should be noted that at physiological pH values the nitrogen atoms in these structures (and in subsequent figures) would be predominantly protonated (see Chapter 32). Additional polyamines found in thermophiles are described in Chapter 5.

Fig 2

Decarboxylases involved in polyamine synthesis. (a) Pyridoxal phosphate (PLP)-dependent decarboxylases [L-1,4-diaminobutyric acid decarboxylase, L-ornithine decarboxylase (ODC), L-lysine decarboxylase and L-arginine decarboxylase]. (b) S-adenosylmethionine decarboxylase, which contains a covalently bound pyruvate group essential for activity.

Fig 3

Aminopropyltransferases involved in polyamine synthesis. The reaction catalyzed by these enzymes involves the attack by the unprotonated terminal N of the amine substrate on the methylene C atom adjacent to the sulfonium center of the dcAdoMet aminopropyl donor. The deprotonation of the attacking N, which is facilitated by residues in the enzyme, and the positive charge on the sulfonium S of dcAdoMet allow the reaction to proceed forming the polyamine product. The reactions shown have all been demonstrated by purified aminopropyltransferases. Other members of this family of enzymes may occur to bring about the synthesis of longer chain polyamines.

Fig 4

Condensation reactions forming polyamines from L-aspartic-β-semialdehyde. Reaction of L-aspartic–β-semialdehyde with putrescine or 1,3-diaminopropane by carboxynorspermidine synthase forms carboxyspermidine or carboxynorspermidine, which are decarboxylated by carboxynorspermidine decarboxylase to form spermidine or sym-norspermidine, respectively.

Fig 5

Synthesis of sym-homospermine and of hypusine. sym-Homospermine can be formed from two molecules of putrescine or from putrescine and spermidine as shown in (a). In both cases, NAD is needed for hydrogen extraction, but is regenerated in the second half of the reaction. The reaction using spermidine and putrescine, which also generates 1,3-diaminopropane, is similar to that used for the hypusine modification of eIF5A shown in (b). In this case, a lysine residue in eIF5A is used instead of putrescine forming deoxyhypusine in eIF5A and free 1,3-diaminopropane. A second enzyme hydroxylates the deoxyhypusine to form the complete hypusine modification (see Chapters 12 and 13 for more details of the reactions forming hypusine).

Fig 6

Reactions catalyzed by SSAT.

Fig 7

Reactions catalyzed by APAO and SMO. APAO has a strong preference for N¹-acetylated polyamines formed by SSAT releasing N-acetyl-3-aminopropanal and SMO is specific for spermine releasing 3-aminopropanal. Both reactions also generate hydrogen peroxide.