Porphyria is a disease that is caused by defects in the enzyme pathway that produces heme, a critical iron compound found throughout the body, most notably in red blood cells. The disease might have been the culprit behind the "madness" of King George III of England.
Bruce Spiegelman of the Dana-Farber Cancer Institute and Harvard Medical School showed that fasting increases levels of a metabolic protein called PGC-1a. The "starvation" signal that fasting sends throughout the body prompts PGC-1a to jumpstart the process of creating glucose from scratch in the liver.
However, PGC-1a also regulates the activity of an enzyme called ALAS-1, the first key enzyme in the heme production pathway. The higher levels of PGC-1a produce higher levels of ALAS-1, leading to a toxic buildup of precursor heme molecules, the researchers found.
The findings are published in the journal Cell.