Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibite...

The lead enzymes of polyamine biosynthesis, i.e. ornithine decarboxylase (ODC) and arginine decarboxylase (ADC), were not detected in Toxoplasma gondii [the limit of detection for ODC and ADC was 5 pmol min(-1) (mg protein)(-1)], indicating that T. gondii lacks a forward-directed polyamine biosynthetic pathway, and is therefore a polyamine auxotroph. The biochemical results were supported by re...

Elevated polyamine levels are characteristic of many types of neoplastic cells and tissues. We demonstrate that in transgenic mice overexpressing ornithine decarboxylase in skin, changes in tissue polyamine levels, particularly putrescine, control the development and maintenance of the neoplastic phenotype. A specific inhibitor of the transgene, alpha-difluoromethylornithine (DFMO), reversibly ...

One hundred ninety patients with a variety of tumor presented within a specified time period and fit a specified protocol. Multiple serial urinary putrescine, spermidine, and spermine levels were obtained in these patients, and their disease activity over time, defined as either active or nonactive, was determined by clinical examination, the results of laboratory tests, and radiological criter...

The polyamine pathway has an essential role in many cellular functions and has been implicated in several pathological conditions. Accumulating evidence suggests that the polyamine system also plays a role in the etiology and pathology of mental disorders. Alterations in the expression and activity of polyamine metabolic enzymes, as well as changes in the levels of the individual polyamines, ha...

The rate of polypeptide chain elongation during steady-state, polyamine-limited growth of a mutant of Escherichia coli was measured by two independent techniques. Analysis of polysome patterns gave values of 17.5 and 9.5 amino acids per s at 37 C in unstarved and polyamine-limited cells, respectively. From the kinetics of entry of labeled amino acids into polypeptides of defined molecular weigh...

Spermidine/spermine-N(1)-acetyltransferase (SSAT) regulates cellular polyamine content. Its acetylated products are either excreted from the cell or oxidized by acetylpolyamine oxidase. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. SSAT is very highly regulated. Its content is adjusted in response to ...

Pegg AE. Spermidine/spermine-N-acetyltransferase: a key metabolic regulator. Am J Physiol Endocrinol Metab 294: E995–E1010, 2008. First published March 18, 2008; doi:10.1152/ajpendo.90217.2008.—Spermidine/spermine-N-acetyltransferase (SSAT) regulates cellular polyamine content. Its acetylated products are either excreted from the cell or oxidized by acetylpolyamine oxidase. Since polyamines pla...

Amifostine metabolites WR-1065 and the disulfide WR-33278 are thiol-containing polyamine analogues with potent radio- and chemoprotective properties. Some studies suggest that amifostine exerts differential cytoprotection in normal versus neoplastic tissues, but this finding remains controversial. To assess the role of the polyamine transport system in radioprotection by amifostine derivatives,...

A superinduction of the polyamine catabolic enzyme, spermidine/spermine N1-acetyltransferase (SSAT) accompanies the phenotype-specific cytotoxic response to a class of antitumor polyamine analogues in several important human solid tumor models. A highly specific antiserum against the human SSAT protein has been developed. Using this antiserum we demonstrate that polyamine analogue treatment in ...