Excessive cysteine, H2S and PPI
I made an interesting “discovery” after connecting several “dots”.
It seems it’s possible to have excess of cysteine in the cell, and when that happens, the cell activates a disposal pathway, which converts cysteine to 3-mercaptopyruvate first (by CAT), and then to hydrogen sulfide - H2S (by MPST).
The problem with excess H2S is that not only it inhibits Complex 3 in the electron transport chain, it also increases production of sulfite which needs detoxification, and interferes with neurotransmission.
Inhibition of Complex 3 by excess H2S can also trigger RET (Reverse Electron Transport) and RET is a very big source of oxidative stress - it’s so strong it can kill pathogens and cancer cells (e.g. melatonin triggers RET in cancer cells and kills them).
Excessive level of H2S is implicated in lowered Prepulse Inhibition (PPI) - that is, a person is easily startled. Some types of schizophrenia also show elevated H2S.
So, when Nrf2 is overactive because the cell is trying to get rid of something or to lower high oxidative stress, it’s possible to end up with high level of cysteine which is not converted into GSH at sufficient rate.
That high cysteine will elevate H2S, causing neurological problems and impaired PPI.