BChE – Pesticides, Parkinson’s, and Potatoes

The BCHE gene codes for the butyrylcholinesterase enzyme. The BChE enzyme is found in the plasma of the blood. It is a cholinesterase which breaks apart choline esters, such as acetylcholine.

Acetylcholinesterase is a similar enzyme that is responsible for breaking down the neurotransmitter, acetylcholine in the synapses of nerves. Think of it as the ‘off switch’ for stopping a neuron from firing repeatedly.

Genetic variants of the BChE gene decrease the enzyme’s activity. This can lead to various and seemingly unconnected consequences…  such as an increased risk for Parkinson’s or a food sensitivity to potatoes.

What does butyrylcholinesterase do in the body?

Butyrylcholinesterase (BChE) can breakdown acetylcholine (similarly to acetylcholinesterase). Since it is found in the bloodstream, though, it doesn’t act within neurons like acetylcholinesterase (AChE) does.

In the synapse of a neuron, acetylcholine causes it to fire, contracting a muscle. AChE breaks down the acetylcholine, letting the muscle relax. This all happens in an instance.

BChE levels become important when exposed to certain types of anesthesia. It controls the rate for the breakdown of succinylcholine, which is a muscle relaxant used during surgery.

BChE also plays a role in the cholinergic anti-inflammatory system. This is a one-way system by which the brain can signal and control the immune response through the vagus nerve.  Macrophages have acetylcholine receptors on their surface, and acetylcholine can then initiate part of the immune response. AChE and BChE can then turn off the immune activation when it is no longer needed.  [ref]

AChE and BChE inactivating acetylcholine which was released from the vagus nerve and acted on a macrophage. Creative Commons license. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100123/

BChE, being in the plasma, can be important in the immune response, especially when AChE is inhibited.

Too much inhibition of AChE results in death. Muscles need to relax – especially those controlling respiration – and excessive inhibition of AChE causes asphyxiation.

AChE inhibitors are a type of medication used in Alzheimer’s disease and glaucoma in very controlled amounts. They can also be used with anesthesia. Snake venom and the nerve gases, sarin and VX, are also AChE inhibitors. And pesticides such as organophosphates and carbamates are AChE inhibitors.

Can pesticides cause Parkinson’s?

Organophosphates are a class of insecticide that is commonly used in agriculture, veterinarian use, home pest control, and for mosquito control. They are the most commonly used type of pesticide.

Specifically, organophosphates include:[ref][ref][ref][ref]

  • malathion (lice, mosquitos)
  • chlorpyrifos (worms, termites)
  • parathion (banned in a lot of countries),
  • diazinon (agricultural insecticide)
  • fenitrothion (chewing and sucking insects)
  • dichlorvos,
  • ethion

Carbamates are another commonly used type of insecticide. Carbamyl (Sevin) is carbamate that is widely used as an insecticide in home and agricultural use.

Organophosphates and carbamates work to kill insects by inhibiting AChE.  Organophosphates are irreversible ACheE inhibitors, while carbamates are less toxic and reversible.

Pesticide exposure has long been linked to Parkinson’s disease. Chlorpyrifos and other organophosphates increase the risk of Parkinson’s disease, depending on the amount of exposure and the genetic variants the person carries. [ref][ref][ref]

More importantly, one of those genetic variants that increase the risk of Parkinson’s due to pesticide exposure is in the BChE gene.

What do potatoes have to do with BChE?

So how do potatoes relate to pesticides and Parkinson’s?

One component of potatoes is a glycoalkaloid compound called α-solanine. The compound is found in the leaves and stems as well as in the tuber that we eat. When potatoes are exposed to light, they turn green due to increased α-solanine. (Green potatoes are toxic – don’t eat them!)[ref]

Potatoes are part of the nightshade family. All of the nightshade family produces varying amounts of glycoalkaloids, which are AChE inhibitors. [ref][ref]

Edible nightshades include potatoes, tomatoes, eggplant, and peppers.

It is theorized that BChE variants interact with the alkaloid compounds in nightshades — but that depends a lot on the amount eaten along with other possible AChE inhibitors. [ref]

When is cholinesterase inhibition a good thing?

While too much of a cholinesterase inhibitor is obviously bad (death is never a good side-effect), a minor inhibition of cholinesterases can be beneficial in some circumstances.

Extending the time that a neuron is exposed to acetylcholine can be beneficial in some cases of Alzheimer’s disease. It also can increase REM sleep, which could be beneficial at times in relation to learning and memory. Cholinesterase inhibitors are also sometimes prescribed for schizophrenia. [ref][ref]

The dose makes the poison is a well-known saying. The right amount of cholinesterase inhibition can be beneficial in certain circumstances. Which leads me to think that carrying a genetic variant that decreases BChE could be beneficial in some ways – and thus explains why a BChE variant that mildly decreases enzyme function is common in the human population.


Genetic Variants of the BChE gene:

The K-variant of BChE decreases the production of the enzyme by 33%. This is a fairly common variant, and up to 30% of some populations carry the k-variant.

Check your genetic data for rs1803274 (23andMe v4, v5):

  • C/C: normal
  • C/T: one copy of the K-variant, decreased BChE, possibly more sensitive to nightshades, increased risk of Parkinson’s with organophosphate exposure
  • TT: two copies of the K-variant, decreased BChE, possibly sensitive to nightshades, increased risk of Parkinson’s with organophosphate exposure [ref][ref][ref]

The A-variant is a more severe change in the BChE enzyme function. About 2% – 5% of some populations carry one copy of the A-variant.

Check your genetic data for rs1799807 (23andMe v4, v5; AncestryDNA):

  • T/T: normal
  • C/T: one copy of A-variant, may have delayed recovery from succinylcholine, increased risk of leprosy [ref][ref][ref]
  • C/C: two copies of A-variant (very rare)

Lifehacks

If you carry one of the BChE variants, you should avoid exposure to nerve gas…

Avoiding Organophosphates

Parkinson’s risk is significantly increased in people with the BChE K-variant and exposure to organophosphates. Eating organic, watching your exposure to pesticides (such as spraying for mosquitos), and avoid using pesticides in your home can reduce your exposure to organophosphates.

If you are interested in knowing which pesticides are commonly detected on foods in the US by the FDA, check out the What’s On My Food website.  The Environmental Working Group puts out a yearly list of the fruits and vegetables found with the most pesticide residue.

Try Eliminating Nightshades

The alkaloids in nightshades are theorized to cause some people to have aching joints and muscle stiffness. These alkaloids interact with the BChE enzyme and carriers of the variants may be more likely to have problems with excessive nightshade intake.

An easy way to know if this is a problem for you is to stop eating nightshades (potatoes, tomatoes, peppers, eggplant, goji berries) for a few days. See how you feel.  Then eat a potato with the skin on it. Perhaps top it with some salsa…

Removing the skins of potatoes (and especially the eyes) cuts down on the alkaloid content. Ripe tomatoes have significantly less alkaloid content (alpha-tomatine) than green tomatoes.  [ref]

Anesthesia complications:

People carrying the BChE k-variant have a delayed recovery from succinylcholine which is as a muscle relaxant when intubating patients under anesthesia. This can cause a delay in returning to normal function (a problem when that normal function involves breathing) But while the response is delayed, it isn’t by much in people who are heterozygous for the K-variant (less than a minute on average).  [ref]

The A-variant is linked to longer delays in returning to normal when succinylcholine is used. This can be more serious and you should tell your doctor if you carry the A-variant and are going to have surgery. The combo of the K-variant and the A variant can lead to more serious complications with succinylcholine.[ref][ref][ref]

Alzheimer’s:

Alzheimer’s risk may be increased in people carrying the BChE K-variant. And people who are homozygous for the K-variant may have a negative response to AChE inhibitors for Alzheimer’s disease. In fact, BChE k-variant carriers had worsening symptoms with the medication donepezil.[ref][ref]

More to read:

Gulf War Illness: Genetic susceptibility and current research

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