Spermine synthase activity affects the content of decarboxylated S-adenosylmethionine.

dcAdoMet (decarboxylated S-adenosylmethionine) is an essential intermediate in the synthesis of polyamines. Its content is normally very low, amounting to less than 5% of that of S-adenosylmethionine itself. It was found that in mice lacking spermine synthase there was a large increase in dcAdoMet and that overexpression of spermine synthase reduced the amount of this nucleoside. There was also an increase in dcAdoMet in cells derived from patients with Snyder-Robinson syndrome, a rare X-linked recessive human disease caused by SMS gene mutations that greatly reduce the content of spermine synthase. These results suggest that there is an inverse relationship between the amount of spermine synthase protein and the content of dcAdoMet and raise the possibility that some of the abnormalities seen in mammals deficient in spermine synthase might be due to changes in dcAdoMet pools.

Partial deletion of both the spermine synthase gene and the Pex gene in the X-linked hypophosphatemic, gyro (Gy) mouse.

Gy, along with Hyp, is a dominant mutation of the normal gene Pex causing X-linked hypophosphatemia in the mouse. Hemizygous Gy male mice, however, have greater defects in survival, bodily growth, skeletal mineralization, and neurological function than those found in heterozygous Gy females or in Hyp mice. Since the gene for spermine synthase is immediately upstream of the homologous human gene PEX, we compared the effects of the Gy and Hyp mutations on both the spermine synthase gene and the Pex gene. Barely detectable levels of spermine (< 5% of normal) with elevated levels of its precursor, spermidine, were found in organs of Gy male mice compared to normal male littermates. Neither Gy females nor Hyp male mice were significantly affected. Four missing introns of the spermine synthase gene were identified in Gy male mice, suggesting extensive gene disruption. A pseudogene for spermine synthase was also identified in the mouse genome. Pex mRNA was found in several but not all tissues studied in adult normal mice. Pex mRNA was altered in both Gy and Hyp mice. All male Hyp mice were lacking the 3' end of the Pex message, whereas all male Gy mice were deficient at the 5' end. In summary, the Gy mutation is associated with a recessively expressed mutation of the spermine synthase gene, leading to spermine deficiency, and a dominantly expressed mutation of the Pex gene, leading to hypophosphatemia. Alterations in two contiguous genes in Gy may explain the additional phenotypic abnormalities present in the Gy male mouse.

2,4-Dichlorophenoxyacetic acid effects on polyamine biosynthesis.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide extensively used in agriculture. It was considered of interest to study its toxicity on animal cells. We had previously determined that 1 mM 2,4-D can inhibit cell growth, DNA and protein synthesis of cultured Chinese hamster ovary cells (CHO) with cell accumulation in the G1/S interphase of the cell cycle. The present work examined the effects of 2,4-D on polyamine biosynthesis. The results suggest some possible mechanism of the herbicide's toxic effects on animal cells.