Glyphosate Blocks Enzyme Function In Plants, Fungi, Bacteria, Mammals

Glyphosate Blocks Enzyme Function In Plants, Fungi, Bacteria, Mammals

Xylem, Phloem, ESPS, Shikimate Pathway, Gastrointestinal Tract, Gut Biome, Amino Acids, Proteins, and the Building Blocks Of Life,

Vs

Glyphosate Based Herbicides:

Roundup and Ranger Pro

UPDATE 06212022 Summer Solstice

Just last week… the EPA was court ordered to review its 2020 determination that Glyphosate ”was not likely to be carcinogenic to humans”.

The 9th Circuit (appeals court) made clear the agency cannot continue to delay a process that could finally result in restrictions on glyphosate’s usage. The panel concluded that the EPA’s determination that glyphosate was not likely to be carcinogenic was not supported by substantial evidence,” said the ruling.” (06212022)

[https://www.agriculture.com/news/business/appeals-court-tells-epa-to-consider-anew-if-glyphosate-is-carcinogenic]

Turns out, we humans are not so different than the plants and bacteria around us.

Most all mammals on the planet, have a symbiotic relationship with various gut microbes, or flora – which are bacteria that reside in their gastrointestinal tract – for the purpose of absorption of nutrients released in digestion.

This post specifically addresses known pathways of documented illnesses reflected in a growing body of research linking the inhibition of the Shikimate Pathway – by glyphosate – to health impacts in kids, parents, babies, dogs, cats, trees, plants, and wildlife, through chronic exposures weighted by the widespread use of glyphosate based herbicides. 

Glyphosate is a non-selective herbicide designed to kill grasses and broad leaf plants, which like trees, are vascular plants. 

Glyphosate targets emergent vegetation – grasses and broadleaf – by interfering with the Shikimate pathway, blocking a particular enzyme. 

Glyphosate based herbicides kill plants by inhibiting an enzyme called EPSPS, which is part of a well-known series of biochemical reactions known as the “shikimate pathway”. The shikimate pathway is responsible for the synthesis of certain amino acids that are vital for the production of proteins, which are the building blocks of life. 

“Thus when the synthesis of the amino acids is blocked by glyphosate’s inhibition of EPSPS, the plant dies.”

“Humans and other animals do not have the shikimate pathway in the cells that make up their bodies, so industry and regulators have claimed that glyphosate is non-toxic to humans. But many strains of gut bacteria of the human gastrointestinal tract, do have the shikimate pathway, leading to debate as to whether Roundup and glyphosate could affect the gut microbiome. Imbalances in gut bacteria have been linked with many diseases, including cancer, diabetes, obesity, and depression.”

How do glyphosate and glyphosate-based herbicides disrupt the human gut microbiome?

The functions of the shikimate pathway in bacteria, and fungi, are the same as with vascular plants, that of being responsible for the synthesis of aromatic amino acids that are vital for the production of proteins, the building blocks of life.

“A 2019 peer-reviewed study in rats provided the first definitive proof that glyphosate and Roundup can inhibit the series of biochemical reactions known as the “shikimate pathway” in the gut microbiome (bacterial population) and can cause alterations in the abundance of certain bacteria at regulatory-permitted (assumed safe) levels of exposure. The shikimate pathway is responsible for the synthesis of aromatic amino acids that are vital for the production of proteins, the building blocks of life. Studies in rats are generally accepted to be relevant to humans.”

“The study, conducted by an international team of scientists based in London, France, Italy, and the Netherlands, and led by Dr Michael Antoniou of King’s College London, has been posted on the open peer-review site BioRxiv, pending publication in a peer-reviewed journal.”

“Scientists had already hypothesized that glyphosate herbicides could inhibit the EPSPS enzyme of the shikimate pathway in gut bacteria, leading to imbalance in the microbiome and thence to harmful effects on health.“

“However, proof that glyphosate herbicides can inhibit the EPSPS enzyme and the shikimate pathway in gut bacteria had been lacking until now. The new study proves beyond doubt that this does indeed happen.”

(2019 research footnotes covering the above 4 paragraphs/section follow)

3.  Mesnage R et al (2019). Shotgun metagenomics and metabolomics reveal glyphosate alters the gut microbiome of Sprague-Dawley rats by inhibiting the shikimate pathway. BioRxiv. doi: [https://doi.org/10.1101/870105]

4.  See the Final addendum to the Renewal Assessment Report on glyphosate [https://echa.europa.eu/documents/10162/13626/renewal_assessment_report_addenda_en.pdf] (October 2015), p23. Rapporteur Member State Germany and co-rapporteur Member State Slovakia state, based on industry claims, “Action at the shikimic acid pathway is unique to glyphosate and the absence of this pathway in animals is an important factor of its low vertebrate toxicity.”

5.  Zmora N et al (2019) You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol. 16: 35-56. [https://www.nature.com/articles/s41575-018-0061-2?draft=collection]

[https://gmoscience.org/2020/01/15/glyphosate-and-roundup-disrupt-the-gut-microbiome-by-inhibiting-the-shikimate-pathway/]

Glyphosate is thought to be safe to use because the shikimate pathway is found only in plants, fungi and bacteria. 

“However, glyphosate may have a strong impact on bacterial species in the human gut microbiome, and several recent studies have shown that perturbations in the human gut microbiome are connected to many diseases. Therefore, the widespread use of glyphosate may have a strong effect on gut microbiomes as well as on human health.”

[https://clinicalnews.org/2020/11/20/glyphosate-and-the-shikimate-pathway/amp/]

“The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.”

[https://pubmed.ncbi.nlm.nih.gov/15012217/]

Manganese, Anxiety, Autism

The pre-eminent 2015 research titled:

“Glyphosate, Pathways To Modern Diseases III: Manganese, Neurological Diseases, And Associated Pathologies” concluded; “that glyphosate’s disruption of Manganese homeostasis can lead to extreme sensitivity to variations in Mn bioavailability: While Mn deficiency in the blood leads to impairment of several Mn dependent enzymes, in contrast, excess Mn readily accumulates in the liver and in the brainstem due to the liver’s impaired ability to export it in the bile acids. This pathology can lead to liver damage and PD. Mn depletion in the gut due to chelation by glyphosate selectively affects Lactobacillus, leading to increased anxiety via the gut–brain access. Both low Lactobacillus levels in the gut and anxiety syndrome are known features of autism, and Lactobacillus probiotic treatments have been shown to alleviate anxiety. “

“Glyphosate is the most widely used herbicide on the planet, in part because of its perceived low toxicity to humans. In this paper, we propose that glyphosate’s chelation of Manganese (Mn) working together with other known effects of glyphosate such as CYP enzyme suppression and depletion of derivatives of the shikimate pathway in microorganisms, may explain the recent increase in incidence of multiple neurological diseases and other pathologies. “

“Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup®-Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup®, has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer’s disease (AD), depression, anxiety syndrome, Parkinson’s disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency.”

“Increased incidence of Salmonella poisoning may also be attributed to glyphosate, through its impairment of bile acid synthesis.”

“Low Mn bioavailability from the blood supply to the brain leads to impaired function of glutamine synthase and a build-up of glutamate and ammonia in the brain, both of which are neurotoxic. Excess brain glutamate and ammonia are associated with many neurological diseases.”

“Many diseases and conditions are currently on the rise in step with glyphosate usage in agriculture, particularly on GM crops of corn and soy. These include autism, AD, PD, anxiety disorder, osteoporosis, inflammatory bowel disease, renal lithiasis, osteomalacia, cholestasis, thyroid dysfunction, and infertility.”

“All of these conditions can be substantially explained by the dysregulation of Mn utilization in the body due to glyphosate.”

*Article contains over 160 footnotes

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/#__ffn_sectitle]


The Shikimate Pathway In Bacteria, Our Gut Microbiome, And Effects Of Glyphosate

Continuing on the subject of the human gastrointestinal digestive-tract associated microbes; our own micro-flora of bacteria, are referred to as the gut microbiome. 

The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physiology, and immune function. Imbalance of the normal gut microbiota have been linked with gastrointestinal conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and wider systemic manifestations of disease such as obesity, type 2 diabetes, and atopy.

“In a healthy state, the gut microbiota have myriad positive functions, including energy recovery from metabolism of nondigestible components of foods, protection of a host from pathogenic invasion, and modulation of the immune system. A dysbiotic state of the gut microbiota is becoming recognized as an environmental factor that interacts with a host’s metabolism and has a role in pathological conditions, both systemic—obesity, diabetes, and atopy—and gut-related IBS and IBD, although the specific contribution of the gut microbiota to these diseases is unclear.” 2014

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566439/]


Glyphosate and Roundup Proven to Disrupt Gut Microbiome by Inhibiting Shikimate Pathway 12112019

“The primary mechanism of how glyphosate herbicides kill plants is by inhibiting an enzyme called EPSPS, which is part of a biochemical pathway known as the shikimate pathway. The shikimate pathway is responsible for the synthesis of certain aromatic amino acids that are vital for the production of proteins, the building blocks of life. Thus when the synthesis of the aromatic amino acids is blocked by glyphosate inhibition of EPSPS, the plant dies. “

“Humans and animals do not have the shikimate pathway, so industry and regulators have claimed that glyphosate is nontoxic to humans. 

“However, many strains of gut bacteria do have the shikimate pathway, leading to much debate about whether Roundup and glyphosate could affect the gut microbiome (bacterial populations). Imbalances in gut bacteria have been found to be linked with many diseases, including cancer, type 2 diabetes, obesity, and depression.”

[https://www.organicconsumers.org/news/glyphosate-and-roundup-proven-disrupt-gut-microbiome-inhibiting-shikimate-pathway]

The following are excerpts from a review of “Glyphosate, Pathways to Modern Diseases IV: Cancer and Related Pathologies,” by Anthony Samsel and Stephanie Seneff at Deerfield NH and MIT, respectively.

[https://riordanclinic.org/2018/11/glyphosate-does-it-provide-a-pathway-to-modern-disease/]

“Further problems in animals or humans arise from the activity of glyphosate and one of its metabolites in the gut flora. In rats, as well as humans, the gut flora can manufacture folate, an important nutrient, which neither rats nor humans synthesize on their own. As noted above, the shimitake pathway is shut down in plants and bacteria by glyphosate. So folate deficiency can arise from impairment of this pathway in our gut flora. Several tumors can be induced in liver and other organs due to folate deficiency.”

“Diabetes is on the rise and often results from bile dysregulation and dysbiosis of the gut microbiome, both of which can result from higher glyphosate levels in the food supply. It also marks an increase of inflammation and increased risk of liver cancer and cancers of the intestinal tract. As shown in Monsanto’s data for rats, kidney abnormalities increased in rats. Similarly the rise of kidney disease and kidney failure is on the rise in humans, this increase took a sharp upturn in 2006.”

Samsel A., Seneff S. Glyphosate, pathways to modern diseases IV: cancer and related pathologies. Journal of Biological Physics and Chemistry15(3):121-159 · January 2015.

[https://riordanclinic.org/2018/11/glyphosate-does-it-provide-a-pathway-to-modern-disease/]

It would appear that Glyphosate Based Herbicides play a role in the increasing incidents of a variety of degenerative diseases including cancer in both animals and humans through various mechanisms.

Documentation on this site, provides a piece of the puzzle, a piece of the picture, and with just a little more of the larger National picture; one can understand how Sacramento Department of Paks and Recreation by it’s overuse of Ranger Pro Glyphosate Based Herbicide would fall into the EPA category of “main risk drivers” as described in the recent EPA Biological Evaluation for Glyphosate, late last year. 

Final National Level Listed Species Biological Evaluation for Glyphosate

Just 6 months ago, in November 2021, EPA released the final Biological Evaluation assessing risks to listed species from “by-the-label” uses of glyphosate. The term “listed species” refers to those that are federally listed as endangered or threatened, as well as populations and species that are proposed and candidates for listing.”

From the EPA:

“Glyphosate is one of the most widely used herbicides in North America. Glyphosate belongs to the phosphono amino acid class of herbicides and is a foliar, non-selective, systemic herbicide widely used to control weeds in agricultural crops and non-agricultural sites. Glyphosate inhibits an enzyme on the shikimate pathway that is essential for the biosynthesis of some aromatic amino acids in algae, higher plants, bacteria and fungi. Inhibition of this enzyme leads to cell death. Glyphosate is used on a wide variety of agricultural food and feed crops, non-foodfeed crops, for plantationsilviculture uses, and for nursery/greenhouse use.”

“Important non-agricultural uses include applications for noxious and invasive weed control in aquatic systems, pastures and rangelands, public lands, forestry, and rights-of-way applications. Glyphosate is also used for general weed control or for lawn replacement/renovation in commercial, industrial, and residential areas (by homeowners, landscaping operators, etc.”

“…non-agricultural uses being the main risk drivers and the lack of availability and uncertainty in usage data associated with these use sites.”

[https://www3.epa.gov/pesticides/nas/final-herbicide/es-gly.docx]

“It is assumed that the glyphosate salts dissociate rapidly to form glyphosate acid and the counter ion. The main routes of dissipation are microbial degradation under aerobic conditions, and runoff. Glyphosate is expected to reach surface water primarily through spray drift; however, transport in runoff may also occur primarily via sorption of glyphosate-metal complexes to eroded soil. The highest concentrations of glyphosate in surface water are in urban environments and in the vicinity of local use areas.”


Glyphosate Madness in a meme…

PRACTICALLY NON-TOXIC

TECHNICAL GLYPHOSATE

FORMULATED GLYPHOSATE

“Technical glyphosate is practically non-toxic to terrestrial and aquatic animals on an acute exposure basis. Toxicity studies, particularly acute aquatic toxicity studies, show that while some formulated products are less toxic than glyphosate active ingredient alone, others can be up to 2 orders of magnitude more toxic.”

“Formulated glyphosate is moderately to highly toxic to fish, highly to very highly toxic to aquatic invertebrates, moderately toxic to mammals, and slightly toxic to birds on an acute exposure basis. In both terrestrial and aquatic animals, technical and formulated glyphosate demonstrate a variety of growth and reproductive effects at a range of chronic exposure concentrations.”

“Glyphosate has demonstrated adverse effects on growth to both vascular and non-vascular aquatic plants as well as terrestrial plants. There have been over 1,000 reported ecological incidents (involving glyphosate use) for birds, fish, terrestrial invertebrates, and terrestrial plants.”

“…the majority (96% of species and 97% of critical habitats) were considered to have moderate evidence. The majority of the moderate evidence designations were based on non-agricultural uses being the main risk drivers and the lack of availability and uncertainty in usage data associated with these use sites.”

[https://www3.epa.gov/pesticides/nas/final-herbicide/es-gly.docx]

Non-agricultural uses are the main risk drivers; including Non-cultivated, Open Space Developed, Right of Way, Forest Trees and Developed with predicted impacts to species or critical habitats.

(From the EPA Executive Summary)

What that translates to:

Overall, it’s likely to adversely impact 

75 endangered species of mammals,

88 endangered bird species, 

36 endangered amphibian species, 

33 endangered reptile species, 

179 endagngered fish species, 

185 endangered aquatic invertebrates, 

140 endangered terrestrial invertebrates, and 

940 endangered plant species.


June 18, 2022 UPDATE

The U.S. Environmental Protection Agency was ordered by a federal appeals court on Friday to take a fresh look at whether glyphosate, the active ingredient in Bayer’s Roundup weed killer, poses unreasonable risks to humans and the environment.

In a 3-0 decision, the 9th U.S. Circuit Court of Appeals agreed with several environmental, farmworker and food-safety advocacy groups that the EPA did not adequately consider whether glyphosate causes cancer and threatens endangered species.

Circuit Judge Michelle Friedland wrote for the Pasadena, California-based appeals court that the EPA did not properly justify its findings that glyphosate did not threaten human health and was unlikely to be carcinogenic to humans. She also faulted aspects of the agency’s approval process.

[https://www.cnbc.com/2022/06/17/epa-ordered-to-reassess-health-risks-in-bayers-weed-killer-ingredient.html]

“The 9th Circuit (appeals court) made clear the agency cannot continue to delay a process that could finally result in restrictions on glyphosate’s usage,” said the Natural Resources Defense Council. The environmental group along with sued the EPA over its 2020 interim decision that “glyphosate is unlikely to be a human carcinogen” or create health risks if used according to EPA guidelines.”

As to human health risks, the appeals court said EPA’s conclusion “was in tension with parts of the agency’s analysis” and its guidelines. “EPA could not reasonably treat its inability to reach a conclusion about NHL (non-Hodgkin’s lymphoma) risk as consistent with a conclusion that glyphosate is not likely to cause cancer within the meanings of its Cancer Guidelines,” said the court in a four-page summary of its ruling.

“The panel concluded that the EPA’s determination that glyphosate was not likely to be carcinogenic was not supported by substantial evidence,” said the ruling. (06212022)

[https://www.agriculture.com/news/business/appeals-court-tells-epa-to-consider-anew-if-glyphosate-is-carcinogenic]

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Tom DiFiore

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