Gut microbial production of trimethylamine (TMA) from L-carnitine is directly linked to cardiovascular disease. TMA formation is facilitated by carnitine monooxygenase which was proposed as a target for the development of new cardioprotective compounds. Therefore, the molecular understanding of the two-component Rieske-type enzyme from E. coli was intended. The redox cofactors of the reductase YeaX (FMN, plant-type [2Fe-2S] cluster) and of the oxygenase YeaW (Rieske-type [2Fe-2S] and mononuclear [Fe] center) were identified. Compounds meldonium and the garlic-derived molecule allicin were recently shown to suppress microbiota-dependent TMA formation. Based on two independent carnitine monooxygenase activity assays, enzyme inhibition by meldonium or allicin was demonstrated. Subsequently, the molecular interplay of the reductase YeaX and the oxygenase YeaW was addressed. Chimeric carnitine monooxygenase activity was efficiently reconstituted by combining YeaX (or YeaW) with the orthologous oxygenase CntA (or reductase CntB) from Acinetobacter baumannii. Partial conservation of the reductase/oxygenase docking interface was concluded. A structure guided mutagenesis approach was used to further investigate the interaction and electron transfer between YeaX and YeaW. Based on AlphaFold structure predictions, a total of 28 site-directed variants of YeaX and YeaW were kinetically analyzed. Functional relevance of YeaX residues Arg271, Lys313 and Asp320 was concluded. Concerning YeaW, a docking surface centered around residues Arg83, Lys104 and Lys117 was hypothesized. The presented results might contribute to the development of TMA-lowering strategies that could reduce the risk for cardiovascular disease.

By means of the vibrating reed technique, measurements of internal friction have been performed in the temperature range of 120 K < T < Tg (= glass temperature) on two amorphous alloys, each produced as ribbon and bulk material. The different contents of free volume result in an only slight shift of the onset of irreversible structural relaxation to lower temperatures (i.e., lower activation energies) for the ribbons, while considerably different amounts of structural relaxation occur. After correcting for the thermoelastic effect, the reversible structural relaxation, i.e., an approximately exponential increase of damping with rising temperature, is well described by KWW kinetics (β ≈ 0.3). For the Zr-based alloy only, a clear relaxation peak occurs in the range from 270 K to 320 K (for the first flexural vibration mode between 100 Hz and 400 Hz) induced by hydrogenation. In addition, the effect of plastic deformation on the damping behavior by cold rolling of the bulk materials has been examined.

Two different types of metallic glasses, a metal-metal-based and a metal-metalloid-based one, in both bulk and ribbon form (i.e., produced with very different quenching rates) are compared with respect to their structural relaxation behavior during continuous heating (2 K/min) in a vibrating-reed set-up (frequencies 0.2–5 kHz). The variation of damping as a function of temperature, time, and strain amplitude is shown as a measure of the content of structural relaxation centers, whose nature is studied by means of artificially introduced irregularities into the amorphous structure (i.e., by cold rolling and by hydrogen charging). The results indicate that the hydrogen damping peak, which is only observed in the Zr-based glass, is more probably due to hydrogen reorientation jumps than due to reorientation of hydrogen-related, dislocation-like distortion fields although the latter cannot be ruled out. A pronounced deformation damping peak could not be found in contrast to earlier results in the literature, probably owing to the selected degrees of deformation.