bims-polyam 2021-01-24 papers

Issue of 2021–01–24
four papers selected by
Sebastian J. Hofer, University of Graz

Mol Microbiol. 2021 Jan 22.

PaeA (ytfl) protects from cadaverine and putrescine stress in Salmonella Typhimurium and E. coli.

Yumi Iwadate, Rouhallah Ramezanifard, Yekaterina A Golubeva, Luke A Fenlon, James M Slauch.

Salmonella and E. coli synthesize, import, and export cadaverine, putrescine, and spermidine to maintain physiological levels and provide pH homeostasis. Both low and high intracellular levels of polyamines confer pleiotropic phenotypes or lethality. Here, we demonstrate that the previously uncharacterized inner membrane protein PaeA (YtfL) is required for reducing cytoplasmic cadaverine and putrescine concentrations. We identified paeA as a gene involved in stationary phase survival when cells were initially grown in acidic medium, in which they produce cadaverine. The paeA mutant is also sensitive to putrescine, but not to spermidine or spermine. Sensitivity to external cadaverine in stationary phase is only observed at pH >8, suggesting that the polyamines need to be deprotonated to passively diffuse into the cell cytoplasm. In the absence of PaeA, intracellular polyamine levels increase and the cells lose viability. Degradation or modification of the polyamines is not relevant. Ectopic expression of the known cadaverine exporter, CadB, in stationary phase partially suppresses the paeA phenotype, and overexpression of PaeA in exponential phase partially complements a cadB mutant grown in acidic medium. These data support the hypothesis that PaeA is a cadaverine/putrescine exporter, reducing potentially toxic levels under certain stress conditions.

Keywords: Salmonella ; cadaverine; polyamines; putrescine; stationary phase

DOI: https://doi.org/10.1111/mmi.14686

Plants (Basel). 2021 Jan 14. pii: E152. [Epub ahead of print]10(1):

Effects of Different Nitrogen Forms and Exogenous Application of Putrescine on Heat Stress of Cauliflower: Photosynthetic Gas Exchange, Mineral Concentration and Lipid Peroxidation.

Jacinta Collado-González, María Carmen Piñero, Ginés Otálora, Josefa López-Marín, Francisco M Del Amor.

This study examines the effect of the exogenous application of polyamine putrescine together with the application of different ratios of nitrate/ammonium (NO3-/NH4+), on the physiology of cauliflower subjected to heat stress. The 50:50 NO3-/NH4+ ratio was the best ratio against heat stress. As a result of the joint application of these compounds, a higher photosynthetic rate, a higher accumulation of both photosynthesis-related compounds and pigments, total proteins, and a change in the status of nutrients were obtained. Particularly, the decrease in content of calcium, chloride and sulphate in plants under heat stress is ameliorated by the ammonium effect. Additionally, it is important to highlight that cauliflower waste contains a higher content of mineral nutrients than floret cauliflower. These effects were more marked in young leaves. Furthermore, a synergistic effect for coping with heat stress between the polyamine and the nutritional treatment was observed. For this, both the application of putrescine and the feeding of plants with a 50:50 NO3-/NH4+ ratio before heat stress is proposed for the first time as an agricultural practice for increasing the thermotolerance of cauliflower cv Moonshine. On the other hand, due to the lower lipid peroxidation rate obtained in cauliflower leaves, these plants could be used for health purposes as ointments or other nutraceutical products, making the cultivation of this kind of cruciferous more sustainable.

Keywords: cauliflower waste; combined stress; heat stress; nitrogen forms; plant nutrition; polyamines

DOI: https://doi.org/10.3390/plants10010152

Mol Genet Metab. 2021 Jan 11. pii: S1096-7192(21)00004-4. [Epub ahead of print]

Derangement of hepatic polyamine, folate, and methionine cycle metabolism in cystathionine beta-synthase-deficient homocystinuria in the presence and absence of treatment: Possible implications for pathogenesis.

Kenneth N Maclean, Hua Jiang, Whitney N Phinney, Bailey M Mclagan, James R Roede, Sally P Stabler.

Cystathionine beta-synthase deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. Our knowledge of the metabolic changes induced in HCU are based almost exclusively on data derived from plasma. In the present study, we present a comprehensive analysis on the effects of HCU upon the hepatic metabolites and enzyme expression levels of the methionine-folate cycles in a mouse model of HCU. HCU induced a 10-fold increase in hepatic total homocysteine and in contrast to plasma, this metabolite was only lowered by approximately 20% by betaine treatment indicating that this toxic metabolite remains unacceptably elevated. Hepatic methionine, S-adenosylmethionine, S-adenosylhomocysteine, N-acetlymethionine, N-formylmethionine, methionine sulfoxide, S-methylcysteine, serine, N-acetylserine, taurocyamine and N-acetyltaurine levels were also significantly increased by HCU while cysteine, N-acetylcysteine and hypotaurine were all significantly decreased. In terms of polyamine metabolism, HCU significantly decreased spermine and spermidine levels while increasing 5'-methylthioadenosine. Betaine treatment restored normal spermine and spermidine levels but further increased 5'-methylthioadenosine. HCU induced a 2-fold induction in expression of both S-adenosylhomocysteine hydrolase and methylenetetrahydrofolate reductase. Induction of this latter enzyme was accompanied by a 10-fold accumulation of its product, 5-methyl-tetrahydrofolate, with the potential to significantly perturb one‑carbon metabolism. Expression of the cytoplasmic isoform of serine hydroxymethyltransferase was unaffected by HCU but the mitochondrial isoform was repressed indicating differential regulation of one‑carbon metabolism in different sub-cellular compartments. All HCU-induced changes in enzyme expression were completely reversed by either betaine or taurine treatment. Collectively, our data show significant alterations of polyamine, folate and methionine cycle metabolism in HCU hepatic tissues that in some cases, differ significantly from those observed in plasma, and have the potential to contribute to multiple aspects of pathogenesis.

Keywords: Cystathionine beta-synthase; Folate cycle; Homocysteine; Homocystinuria; Methionine cycle; One‑carbon metabolism

DOI: https://doi.org/10.1016/j.ymgme.2021.01.003

FEBS J. 2021 Jan 18.

More than just protein building blocks: How amino acids and related metabolic pathways fuel macrophage polarization.

Markus Kieler, Melanie Hofmann, Gernot Schabbauer.

Macrophages represent the first line of defence in innate immune responses and additionally serve important functions for the regulation of host inflammation and tissue homeostasis. The M1/M2 model describes the two extremes of macrophage polarization states, which can be induced by multiple stimuli, most notably by LPS/IFN-γ and IL-4/IL-13. Historically, the expression of two genes encoding for enzymes, which use the same amino acid as their substrate, iNOS and ARG1, has been used to define classically activated M1 (iNOS) and alternatively activated M2 (ARG1) macrophages. This "arginine dichotomy" has recently become a matter of debate; however, in parallel with the emerging field of immunometabolism it is becoming more and more evident that these two enzymes and their related metabolites are fundamentally involved in the intrinsic regulation of macrophage polarization and function. The aim of this review is to highlight recent advances in macrophage biology and immunometabolism with a specific focus on amino acid metabolism and their related metabolic pathways: urea cycle (arginine), TCA cycle and OXPHOS (glutamine) as well as the one carbon metabolism (serine, glycine).

Keywords: TCA cycle; arginase/iNOS; glutamine; immunometabolism; macrophage polarization; nitric oxide; oxidative phosphorylation; polyamines; serine; α-ketoglutarate

DOI: https://doi.org/10.1111/febs.15715