Figure 3

The synthesis of polyamines and the hypusination of eIF5A. Enzymes are: arginosuccinate lyase (1), arginase (2), ornithine carbamoyl transferase (3), arginosuccinate synthase (4), ornithine decarboxylase (ODC) (5), spermidine synthase (6), spermine synthase (7). Spermine synthase and spermidine synthase also require decarboxylated S-adenosylmethionine which is produced by S-adenosylmethionine decarboxylase. Polyamines catabolism (8) is achieved by spermine/spermidine N¹-acetyltransferase and a peroxisomal flavoprotein polyamine oxidase. The formation of hypusine (N^ε-(4-amino-2-hydroxybutyl)lysine) occurs in two steps. Deoxyhypusine synthase (9) transfers the 4-aminobutyl moiety of spermidine to the ε-amino group of a specific lysine residue of eIF5A. Deoxyhypusine hydroxylase (10) hydroxylates eIF5A-deoxyhypusine. In yeast and mammals, only hypusinated forms of eIF5A are active. DFMO inhibits ODC, the rate limiting enzyme for polyamine synthesis. GC7 inhibits deoxyhypusine synthase (DHS). The polyamines synthetic enzymes, ODC and S-adenosylmethionine decarboxylase are up regulated in response to a decrease in polyamines. Spermine/spermidine N¹-acetyltransferase which mediates the retroconversion of polyamines is up regulated by spermine and spermidine.