Aconitase 1 (ACO1) is an enzyme in the citric acid cycle. Aconitase 1 is a dual function protein. Upon loss of an iron-sulfur cluster ACO1 becomes iron regulatory protein 1 (IRP1). IRP1 affects stability of mRNA transcripts of proteins involved in iron metabolism such as ferritin, DMT1, which is an iron transporter, and ferroportin, which is the only known iron exporter. Increasing iron levels switches IRP1 to ACO1 as IRP1 gains an iron-sulfur cluster. With a 4Fe-4S iron-sulfur cluster ACO1 can participate in the citric acid cycle and generate ATP.
On-off disorders could be are due to wide swings in ACO1/IRP1 and the TCA cycle. Suddenly the TCA cycle is functioning and then the TCA cycle is not functioning while at the same time there are swings in the regulation of iron regulated proteins. Dietary iron could be associated with swings in on-off symptoms.An added wrinkle is that high IRP1 levels adversely affects copper absorption, however, copper is needed for iron metabolism.
I very much like answers that answer everything. On-off symptoms are prominent in lots and lots of illnesses. There is, of course, bipolar disorder but a lot of depressions cycle rapidly and are some of the most difficult depressions to treat. Parkinson’s disease has a very prominent on-off symptoms. In Parkinson’s disease there are indications that iron metabolism is dysregulated. There could be a unitary explanation for cycling disorders.