Covalent Polyamine-Protein Conjugates: Analysis and Distribution

Abstract

Most suggestions as to the biological functions of the polyamines, putrescine, spermidine, and spermine, are based on the observed noncovalent binding of these polycations to nucleic acids, proteins, and phospholipids.^1–3 It was recently shown that polyamines are also present in mammalian tissues and body fluids in covalent association with proteins. Protein modifications in which structural elements of polyamines are involved occur by two pathways. In one of these the amino acid hypusine [N^ε-(4-amino-2-hydroxybutyl)lysine] is formed through transfer of the butylamine moiety of spermidine to the ε-amino group of a protein lysine residue and through subsequent hydroxylation.⁴ In the other polyamines are attached in covalent amide linkage to the γ-carboxyl groups of protein glutamic acid residues. Conjugation of the amines in this manner is catalyzed by transglutaminases, Ca²⁺ -dependent enzymes which promote exchange of primary amines for ammonia at the carboxamide groups of certain glutaminyl residues.^{5, 6} A number of transglutaminases have been identified and they are found widely distributed in mammalian cells and in biological fluids.^{7, 8} These enzymes are responsible for production of ε-(γ-glutamyl)lysine crosslinks that connect protein chains and play a central role in such extracellular events as fibrin clot stabilization and seminal plug formation.^{7, 8}