Glyphosate, the active ingredient in Roundup herbicide, inhibits the shikimate pathway in both plants and bacteria. This pathway is responsible for the production of aromatic amino acids like tryptophan and phenylalanine. When ingested, glyphosate can disrupt gut bacteria in humans by inhibiting this pathway. This can lead to decreased production of important neurotransmitters and signaling molecules as well as vitamin deficiencies. Imbalances in gut bacteria from glyphosate exposure cause similar gastrointestinal issues seen in autism. While not proven, it is possible that disrupting the shikimate pathway through increased glyphosate use could contribute to the symptoms of autism spectrum disorder by impacting amino acid production and microbiome

1. Possible Toxicity of Glyphosate and
Links to Autism
Presented by
Arloe Fontenot
20 April 2015

2. “Half of all children will be autistic by 2025,
warns Senior Research Scientist at MIT…”
• Stephanie Seneff, PhD, has concentrated her research on the
relationship between nutrition and health
• Published over 170 peer-reviewed articles focusing on Alzheimer’s,
autism, cardiovascular disease, as well as impacts of nutritional
deficiencies and environmental toxins on human health
• Has shown a correlation between use of Roundup herbicide and rising
rates of autism
• Glyphosate is a known inhibitor of the Shikimate pathway

3. Primary active ingredient in Monsanto Co.
Roundup herbicide
Not a typical organophosphate but an
aminophoshonic analog of glycine, and does not
inhibit cholinesterase activity
Found in over 750 commercial products sold in
the United States
Shikimate pathway – occurs only in microorganisms and plant cells
Pathway goals: Biosynthesis of 3 aromatic amino acids: tryptophan,
phenylalanine, and tyrosine from phosphenol pyruvate (PEP) and
erythrose 4-phosphate (E4P)
Tryptophan and phenylalanine are both essential aa’s, where
phenylalanine is converted to tyrosine (non-essential).
Tyrosine is converted to L-Dopa, the precursor for monoamine
neurotransmitters dopamine, noradrenaline, and adrenaline
Shikimate Pathway has been referred to as the common aromatic
biosynthetic pathway
Glyphosate’s target enzyme is 5-enolpyruvylshikimate 3-phosphate (EPSP)
synthase, the sixth enzyme of the pathway
Glyphosate occupies the binding site of PEP on the enzyme prohibiting
formation of chorismate
Scientists target this enzyme for many herbicides, and antibiotic and
antipathogenic drugs (Schonbrunn, Kabsch et al, 2000)
Courtesy cell.com

4. Shikimate Pathway (plants and bacteria)
• Two parts, from PEP and E4P to chorismate, which is common to all 3 aromatic amino acids, and
from chorismate to each individual aromatic amino acid
• Seven Common Steps
• Step 1 – Glycolytic intermediate PEP and pentose phosphate pathway intermediate E4P are condensed to a seven-
carbon six-membered heterocyclic compound, 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP)
• Step 2 – Exocyclic C7 on DAHP is substituted for a ringed oxygen to form a highly substituted cyclohexane derivative,
3-dehydroquinate
• Step 3-Step 7 –The five remaining steps introduce a side chain and two of the three double bonds converting the
cyclohexane from step 2 into the benzene ring
• Step 6 (PEP to EPSP) is catalyzed by EPSP synthase, the best studied enzyme of the pathway. The target for
glyphosate herbicide in plants, but inhibits the pathway in microbes also. Plant enzymes have glyphosate K1 values
approx. one order of magnitude lower than microbial enzymes. The high degree of specificity of glyphosate for EPSP
synthase is due to the herbicide binding to the enzyme only in close proximity to shikimate 3-phosphate formed in
step 5, coupled with the product of the enzyme catalyzed reaction, EPSP in step 6, also facilitating glyphosate
binding
• Step 7 – involves 1,4-trans elimination of phosphate from EPSP to form chorismate
• Chorismate is the substrate for Tryptophan, Phenylalanine, and Tyrosine, however when EPSP is inhibited by
glyphosate, chorismate is prohibited from being formed

5. How can a chemical that affects plants and bacteria
induce toxicity in humans?
• When humans ingest small amounts of glyphosate through pesticide residues in food, the Shikimate
pathway is inhibited in human gut bacteria
• The seven steps of the Shikimate pathway are identical in bacteria, so exposure to glyphosate targets
EPSP in intestinal bacterial
• Decrease in synthesis of aromatic amino acids phenylalanine, tryptophan, and tyrosine causing
translational deficits
• Aromatic amino acid repression causes decreases in signaling molecules dopamine, norepinephrine, and
epinephrine, and skin pigment melanin
• Human body contains around 100 trillion flora in the intestines
• Gut or intestinal flora are also responsible for metabolizing undigested carbohydrates, allowing for human
reabsorption of short-chain fatty acids. Also play a role in synthesizing vitamins B and K. Food allergies
such as gluten intolerance and disrupted sulfur metabolism leading to sulfur and sulfate deficiency
• Systemic toxicity caused by disruption of microbial functioning allows for overgrowth of pathogens in the
body
• New research is showing glyphosate synergistically causing toxicity by inhibition of human CYP 450
enzymes coupled with the disruption of aromatic amino acid synthesis, as well as impaired serum sulfate
transport
• This evidence is pointing to glyphosate enhancing damaging effects of other food-borne chemical
residues and other environmental toxins (eg. formaldehyde) by shutting down detoxifying enzymes (CYP)
• Formation of ammonia from microbial breakdown of glyphosate in the human body can lead to brain
inflammation associated with autism and Alzheimer’s disease

6. Links to Autism
• Imbalance in gut flora causes the same type of gastrointestinal disturbances witnessed in
autism spectrum disorder
• Although not a direct linkage has been established, it is possible aromatic amino acid
biosynthetic repression by increased usage of glyphosate-based products may be
responsible for the intellectual disability, difficulties in motor coordination, and physical
health issues such as sleep disturbances and food intolerances leading to autism
Question
How does glyphosate indirectly cause symptoms of Autism spectrum disorder?

7. References
Alliance for Natural Health USA. (2014). Half of All Children Will Be Autistic by 2025, Warns Senior Research Scientist at MIT.
Retrieved from http://www.anh-usa.org/half-of-all-children-will-be-autistic-by-2025-warns-senior-research-scientist-at-mit/
Herrmann, Klaus M. (1995). The Shikimate Pathway: Early Steps in the Biosynthesis of Aromatic Compounds .The Plant Cell.
Vol 7., 907-919. Retrieved from http://www.plantcell.org/content/7/7/907.full.pdf
Mercola, Dr. Joseph. 09 June 2013. Monsanto’s Roundup Herbicide May Be Most Important Factor in Development of Autism
and Other Chronic Disease. Retrieved from http://articles.mercola.com/sites/articles/archive/2013/06/09/monsanto-
roundup-herbicide.aspx
Autism Speaks. What is Autism?. Retrieved from https://www.autismspeaks.org/what-autism