Abstract meaning: the metabolism of glutathione is comparable to a puzzle with too many pieces. (i) reduction of disulfides, hydroperoxides, sultopics and nitrosothioles, (ii) detoxification of adehhydes, xenobiotics and heavy metals, and (iii) synthesis of eicosanoides, steroids and sulphur clumps. In addition, glutathione acts on oxidative deployment of proteins and redox signaling. Here, I try to give an overview of the relevance of glutathione-dependent pathways, with an emphasis on quantitative data. Recent progress: Intracellular redox measurements show that cytosol, nucleus and mitochondria contain very little glutathiothiondisulfide and that oxidative challenges are quickly compensated. Genetic approaches suggest that iron metabolism is at the heart of the glutathione puzzle in yeast. In addition, recent biochemical studies provide new knowledge on glutathione transport processes and decoupling mechanisms. Critical Questions: Which pieces of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can biogegenesis in clusters of sulphur iron, protein oxidation or redox signaling occur at high levels of glutathione? The answers to these questions seem to depend not only on the organism, the type of cell and the sub-cellular matter, but also on different ideologies among researchers. Future Directions: A rational approach to comparing the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, many pieces are still missing and too little is known about the compartment-specific repertoire and the concentration of many metabolites, substrates, enzymes and transporters, as well as rate constants and enzymatic patterns.
Collecting this information may require the development of innovative tools, but it is essential to address potential kinetic competitions and decipher decoupling Analysis of randomly formed puzzle fragments on their chord length distribution There is a current interest in random-phase alcohol proximation (RPA), a “five-tier” density that works for alternative correlation energy. RPA has a complete and accurate exchange and builds correlation using the unoccupied Kohn-Sham orbital. In many cases (single electron gas, jellium surface and free atom), RPA correction is a short-wheeled effect, which is covered by local difssion aproximation (LSDA) or by widespread gradient application (GGA). Non-moving density functions for RPA correction have previously been designed at the LSDA and GGA (RPA) level, but are designed here at the non-local level (RPA) using the van der Waals (vdW-DF) density function of Langreth, Lundqvist and collaborators. While they make important and useful corrections on the total RPA and ionization energies of free atoms, they correct only about 1 kcal/mol the RPA atom energies of the molecules. Therefore, it is mysterious that RPA spray energy sources are on average about 10 kcal/mol lower than the exact values of the experiment.