Aminopropyltransferases use
decarboxylated S-adenosylmethionine as an aminopropyl donor and an
amine acceptor to form
polyamines. This review covers their structure, mechanism of action, inhibition, regulation and function. The best known aminopropyltransferases are
spermidine synthase and
spermine synthase but other members of this family including an N(1)-aminopropylagmatine synthase have been characterized.
Spermidine synthase is an essential gene in eukaryotes and is very widely distributed. Key regions in the active site, which are very highly conserved, were identified by structural studies with
spermidine synthase from Thermotoga maritima bound to
S-adenosyl-1,8-diamino-3-thiooctane, a multisubstrate analog inhibitor. A general mechanism for catalysis by aminopropyltransferases can be proposed based on these studies.
Spermine synthase is less widely distributed and is not essential for growth in yeast. However, Gy mice lacking
spermine synthase have multiple symptoms including a profound growth retardation,
sterility,
deafness, neurological abnormalities and a propensity to
sudden death, which can all be prevented by transgenic expression of
spermine synthase. A large reduction in
spermine synthase in human males due to a splice site variant causes
Snyder-Robinson syndrome with
mental retardation,
hypotonia and skeletal abnormalities.