Effects of antagonists of polyamine metabolism on African trypanosomes

This review outlines the metabolism of polyamines in African trypanosomes and summarizes evidence to indicate that trypanosome polyamine metabolism differs in several important aspects from that of the mammalian host. These differences relate to the halflife, turnover, substrate specificity and regulation of enzymes within the mainstream of polyamine synthesis and the related pathway of transmethylation. The common denominator for the uniqueness of parasite polyamine metabolism concerns S-adenosylmethionine (AdoMet) whose synthesis is unregulated and, upon accumulating in the cell, appears to result in abnormally high transmethylation activity. Similarly, the catabolism of the AdoMet product of polyamine synthesis, methylthioadenosine, is governed by a phosphorylase having broad substrate specificity, and which, if presented with substrate analogs, can generate cytotoxic metabolites.