Intracellular Calcium, Ferroptosis, and Glutamate
RANTES
Arachidonic Acid Pathway Map
Ferroptosis Pathway Map
Holmes Cycle Hypothesis
Toxic environmental factors that we have historically not encountered (epigenetics) cause overstimulation of NOX (NADPH oxidase) enzymes in individuals whose genetic susceptibility amplifies their negative effects.
This leads to the excessive production of superoxide, peroxynitrite, mast cells, histamine, and glutamate.
NOX enzymes use NADPH to generate free radicals, resulting in a phenomenon we call 'NADPH stealing,' thereby reducing the NADPH needed to support Phase I detoxification, nitric oxide production, and the cycling of key antioxidants like glutathione.
In turn, these NOX-generated free radicals stimulate renin, angiotensin I, angiotensin II, aldosterone, IL-6, and NOX, creating a positive feedback loop that results in a self-perpetuating inflammatory vicious cycle known as the 'Holmes Cycle'.
