TL;DR: It is suggested that the cyclic process is necessary for the precise control of cellular polyamine concentrations, as it allows relatively rapid spermine and spermidine concentration changes, in spite of a slow basal turnover rate.
Abstract: Acetylation is a means to decrease the net positive charge of the polyamines and thus liberate polyamines from anionic binding sites. The acetyl derivatives can be removed from the cells by transport and catabolism. Intracellular polyamine metabolism can be formulated as a cyclic process, which explains the transformation of one polyamine into another. As a net result, this pathway metabolizes (in an energy-requiring manner) methionine to 5'-deoxy-5'-methylthioadenosine and beta-alanine, and thus appears to be futile. It is suggested that the cyclic process is necessary for the precise control of cellular polyamine concentrations, as it allows relatively rapid spermine and spermidine concentration changes, in spite of a slow basal turnover rate. For the regulation of cellular polyamine metabolism, two decarboxylases, L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase; the cytosolic acetyl-CoA:spermidine/spermine N1-acetyltransferase; and a polyamine transport system are required. The activity of the nuclear acetyltransferase is assumed to be the rate-limiting enzyme of nuclear polyamine turnover. The complexity and high level of sophistication of polyamine regulation is strong evidence for the important functional significance of the natural polyamines.
TL;DR: Observations indicate that polyamine metabolism is presumably a target in the antiproliferative properties of geraniol, which is enhanced in cancer growth.
Abstract: Geraniol and other monoterpenes found in essential oils of fruits and herbs have been suggested to represent a new class of agents for cancer chemoprevention As a first step in clarifying the mode of action of geraniol on colon carcinogenesis, we studied its effects on the growth of a human colon cancer cell line (Caco-2) Geraniol (400 microM) caused a 70% inhibition of cell growth, with cells accumulating in the S transition phase of the cell cycle, and concomitant inhibition of DNA synthesis No signs of cytotoxicity or apoptosis were detected Geraniol caused a 50% decrease of ornithine decarboxylase activity, a key enzyme of polyamine biosynthesis, which is enhanced in cancer growth This led to a 40% reduction of the intracellular pool of putrescine Geraniol also activated the intracellular catabolism of polyamines, indicated by enhanced polyamine acetylation These observations indicate that polyamine metabolism is presumably a target in the antiproliferative properties of geraniol
TL;DR: Great genetic adaptation was seen at pH 9 than at pH 6, which may explain the lag time required for growth shift to high pH, and the SigH, SigL, and SigW regulons were upregulated at high pH.
Abstract: Acid and base environmental stress responses were investigated in Bacillus subtilis B subtilis AG174 cultures in buffered potassium-modified Luria broth were switched from pH 85 to pH 60 and recovered growth rapidly, whereas cultures switched from pH 60 to pH 85 showed a long lag time Log-phase cultures at pH 60 survived 60 to 100% at pH 45, whereas cells grown at pH 70 survived <15% Cells grown at pH 90 survived 40 to 100% at pH 10, whereas cells grown at pH 70 survived <5% Thus, growth in a moderate acid or base induced adaptation to a more extreme acid or base, respectively Expression indices from Affymetrix chip hybridization were obtained for 4,095 protein-encoding open reading frames of B subtilis grown at external pH 6, pH 7, and pH 9 Growth at pH 6 upregulated acetoin production (alsDS), dehydrogenases (adhA, ald, fdhD, and gabD), and decarboxylases (psd and speA) Acid upregulated malate metabolism (maeN), metal export (czcDO and cadA), oxidative stress (catalase katA; OYE family namA), and the SigX extracytoplasmic stress regulon Growth at pH 9 upregulated arginine catabolism (roc), which generates organic acids, glutamate synthase (gltAB), polyamine acetylation and transport (blt), the K+/H+ antiporter (yhaTU), and cytochrome oxidoreductases (cyd, ctaACE, and qcrC) The SigH, SigL, and SigW regulons were upregulated at high pH Overall, greater genetic adaptation was seen at pH 9 than at pH 6, which may explain the lag time required for growth shift to high pH Low external pH favored dehydrogenases and decarboxylases that may consume acids and generate basic amines, whereas high external pH favored catabolism-generating acids
TL;DR: Results indicate that cellular polyamine levels can be regulated by excretion of spermidine and that the bis(ethyl)spermine derivatives deplete intracellular polyamine content by interference with this process.
TL;DR: The findings are consistent with a paradigm whereby flux is initiated by SSAT acetylation of spermine and particularly spermidine followed by a marked increase in key biosynthetic enzymes.