It also suppresses RuBisCo in plants, which is critical for photosynthesis and is the most common protein in the world [12]. All of these proteins have in common that they bind to phosphate-containing dinucleotides.
Heme Oxygenase in COVID-19
In a previous article in a recent issue of this journal, I presented the argument that glyphosate in biofuels could be a significant factor in inducing acute sensitivity to COVID-19, leading to a downward spiral into a life-threatening situation [13]. Air pollution is a known risk factor for bad outcomes, yet a country like Taiwan with poor air quality in the big cities nonetheless has had only a handful of deaths from COVID-19. Taiwan uses much less glyphosate than the US and does not use any biofuels in its vehicles. I also talked about the unusual lung disease that is showing up in people who use e-cigarettes, which is symptomatically very similar to COVID-19. E-cigarettes make use of glycerol, a by-product of the biofuel industry, as the solvent for the nicotine, and it is likely also contaminated with glyphosate.
It is clear that some COVID-19 cases cascade into a hyperinflammatory state in the blood. This induces an acute thrombotic response, with blood clots appearing throughout the vasculature, eventually leading to multiple organ failure and death. A recent publication suggested that the pathology might be caused by an insufficient production of an enzyme called heme oxygenase 1 (HO-1) [14].
Normally, under conditions of extreme stress, an inflammatory response induces increased production of HO-1, and HO-1 converts heme (the molecule that carries oxygen in hemoglobin) into biliverdin (a green pigment excreted in bile, and an oxidized form of bilirubin), releasing carbon monoxide (a signaling gas that helps tame the inflammation).
HO-1 usually operates in the endoplasmic reticulum, but, under stressful conditions, it moves into the mitochondria. Importantly, along with biliverdin production, it converts three molecules of oxygen into three molecules of water, while converting three molecules of NADPH into NADP+. In other words, it produces deuterium-depleted water in the mitochondria! The restoration of NADPH from NADP+, crucial for sustaining the reaction, depends on an enzyme that glyphosate is known to suppress, namely CYP reductase [15].
Besides reducing the supply of NADPH and interfering with the ability to maintain NADPH in its active, reduced form, how else might glyphosate interfere with HO-1? A highly significant fact is that the enzyme contains two critical glycine residues -- G139 and G143 -- that bind electrostatically to heme and secure it in place to allow the reaction to take place. If either of these glycines is mutated to a different amino acid, the enzyme can no longer successfully carry out its reaction.
The title of a paper published in 2000 clearly states the consequences of losing the first glycine residue: “Replacement of the Distal Glycine 139 Transforms Human Heme Oxygenase-1 into a Peroxidase.” [16] Among the different amino acids that they replaced it with, the one that caused the worst disruption was aspartate.
Aspartate is a very good model for glyphosate, because, like glyphosate, it is considerably larger than glycine and negatively charged. Turning the molecule into a peroxidase would result in the release of redox-active ferryl iron (Fe(IV)) -- a highly oxidized and very dangerous form of iron [17]. Worse than this, the reaction that converts heme to biliverdin is completely blocked, so the mitochondria receive no benefit from the production of DDW.