Clearly glyphosate can’t fit everywhere that glycine can fit. If the neighboring amino acids are big and bulky, glyphosate’s extra methylphosphonate will have nowhere to go. However, one place where it is likely to fit well is in a protein that binds phosphate at the site where phosphate binds.
The methylphosphonate unit can occupy the roomy hole where phosphate in the substrate that binds to the enzyme is supposed to fit. This of course totally prevents the substrate from binding, thus ruining the enzyme’s ability to carry out the reaction it normally achieves [2].
This is exactly what I think happens when glyphosate suppresses the activity of 5- enolpyruvylshikimate-3-phosphate (EPSP) synthase, the enzyme that it blocks in the shikimate pathway to kill plants. There is a highly conserved glycine residue at the site where EPSP synthase binds the phosphate anion in phosphoenolpyruvate (PEP).
Researchers have consistently found that swapping out that glycine for the amino acid alanine (through a mutation in the genetic code for the protein) results in a version of the protein that is completely insensitive to glyphosate’s effects [3].
In fact, they have used this idea to create glyphosate resistance in genetically modified crops. The simplest way to explain glyphosate’s effects is to propose that it displaces glycine in the enzyme, and its bulky methylphosphonate group blocks binding to PEP.
The shikimate pathway produces the three aromatic amino acids, tryptophan, tyrosine, and phenylalanine. Like glycine, these amino acids are members of the elite club of “coding” amino acids that are strung together to make all the proteins of the body according to the DNA code. Human cells are unable to synthesize these amino acids, because they don’t have a shikimate pathway, so they are called “essential.”
We have to acquire them from our diet or rely on our gut microbes to use their shikimate pathway to synthesize them for us, their host. When our food sources or gut microbes are exposed to glyphosate, they become impaired in their ability to supply us with these crucial nutrients, and we can become deficient.
Many biologically active molecules are derived from the products of the shikimate pathway, including the neurotransmitters serotonin, melatonin, dopamine and epinephrine, thyroid hormone, the skin tanning agent melanin and the B vitamins niacin and riboflavin.
Niacin and riboflavin are going to play a central role in the discussion below, which will ultimately lead to an explanation of why glyphosate might cause COVID-19 to be a much more severe disease than it would otherwise be!
Glyphosate