Reactions of proteins with oxidizing lipids: 1. Analytical measurements of lipid oxidation and of amino acid losses in a whey protein-methyl linolenate model system

1. The reactions between protein-bound amino acids and oxidizing lipid were investigated in a whey protein-methyl linolenate (C18.3)-water model system. The extent of fat oxidation was followed by measuring oxygen uptake, hydroperoxide formation and hydrocarbon (ethane and pentane) formation. 2. Significant losses occurred with lysine (up to 71 %), tryptophan (up to 31 %) and histidine (up to 57%). Methionine was extensively oxidized to its sulphoxide but less than 2% was further oxidized to the sulphone. No other amino acids were affected. 3. Increasing storage temperature (20°, 37°, 55°) resulted in an enhancement of fat oxidation reactions and amino acid degradation. 4. Increasing water activity (0.28, 0.65, 0.90) increased losses of lysine and tryptophan but had no influence on the oxidation of methionine, the level of remaining hydroperoxides or 02 uptake. Hydrocarbons were decreased. 5. Limitation of 02 uptake to 1 mol/mol lipid instead of excess 02 (02 uptake about 2.5 mol/mol lipid in 4 weeks) significantly reduced the degradation of lysine and tryptophan but had less influence on the oxidation of methionine. The level of remaining hydroperoxides was increased but hydrocarbons were unaffecte

Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.

Serum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8+ T cells to produce IFN-γ. Whether acetate modulates memory CD8+ T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8+ T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly activating glutaminase, thereby augmenting glutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggered calcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducing immunopathology. This indicates that, during different stages of the immune response, the same metabolite-acetate-induces distinct immunometabolic programs within the same cell type