BChE: Nightshade sensitivity, Anesthesia risk, and more

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.

Why is this important? Genetic variants of the BChE gene decrease this 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 is butyrylcholinesterase (BChE)?

Butyrylcholinesterase (BChE) is an enzyme, which is a type of protein that causes a reaction to happen in the body.

But before we get into BChE, let’s talk a little about AChE…

Acetylcholinesterase (AChE) 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. It’s one of those really important enzymes that you can’t live without. Period.

Getting a little more detailed: In the synapse of a neuron, acetylcholine causes it to fire, contracting a muscle. AChE causes the break down of the acetylcholine, stopping the contractions and letting the muscle relax. This all happens in an instance. Too much inhibition of AChE results in death. Muscles need to relax – especially those controlling respiration – and excessive inhibition of AChE causes asphyxiation.

The butyrylcholinesterase (BChE) enzyme can also break down acetylcholine – similar to acetylcholinesterase. Since BChE is found in the bloodstream, though, it doesn’t act within neurons like acetylcholinesterase (AChE) does.

Not only can BChE bind with acetylcholine, but it can also bind to other substances that inhibit AChE. In this way, BChE is considered a bio scavenger, protecting the body from certain toxicants or poisons. [ref]

It is interesting to note that while there are several different genetic variants that reduce the function of BChE significantly, there are very few genetic mutations that decrease AChE significantly. This is another indication of the AChE enzyme being is for life. [ref]

When is BChE important?

While the functionality of the BChE enzyme used to be in question, recent research shines a lot of light on this molecule.  BChE is important for:

  • recovery from certain types of anesthesia
  • inactivating immune response
  • protecting against nerve agents, snake toxins, and other AChE inhibitors
  • inactivating certain compounds in nightshades
  • modulating the hunger hormone ghrelin

Let’s dig into all of these topics further…

BChE and recovery from anesthesia (succinylcholine)

BChE levels become important when exposed to certain types of anesthesia. The BChE enzyme controls the rate for the breakdown of succinylcholine, which is a muscle relaxant used during surgery. People with genetic variants that significantly decrease the amount of BChE (A-variant, below) can have problems coming out of anesthesia and returning to breathing on their own.

BChE and Macrophages:

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]  BChE, being in the plasma, can be especially important in the immune response.

Below: AChE and BChE inactivating acetylcholine which was released from the vagus nerve and acted on a macrophage. Creative Commons license. 

BChE as a bio scavenger:

Inhibiting AChE is generally bad and often deadly. Thus, researchers think this is one reason why we have a built-in system in which BChE is able to break down toxins in order to protect AChE.

AChE inhibitors include some natural toxins, such as snake venom. The nerve gasses, sarin and VX are also AChE inhibitors. And pesticides such as organophosphates and carbamates are AChE inhibitors.  BChE may act as a bio scavenger in the plasma, breaking down these molecules before they can interfere with nerve transmission and AChE.

In the past (1940s-’60s), tests were done on volunteers in the military to determine the effects of low levels of the nerve agents that target AChE. These human tests pointed out big differences between individuals in the response to nerve gas, and the differences seem to be tied to genetic variants in the BChE gene. Modern animal and cell studies have confirmed this, since we thankfully no longer test nerve gas on people![ref]

Organophosphates and BChE

Organophosphates are a class of insecticide that is commonly used in agriculture, veterinarian use, home pest control, and 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.

BChE may act as a bio scavenger to protect AChE from being impacted by organophosphates and other substances.[ref]  People with BChE genetic variants may be more prone to detrimental effects from exposure to organophosphates. [ref]

BChE, organophosphates, and Parkinson’s risk:

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 the genetic variants that increase the risk of Parkinson’s due to pesticide exposure is in the BChE gene. (below)

BChE genetic variants = (possible) sensitivity to nightshades?

The edible nightshade vegetables include potatoes, tomatoes, eggplant, and peppers.  All of the nightshade family produces varying amounts of glycoalkaloids, which are AChE and BChE inhibitors. The plants produce these compounds to repel insects.[ref][ref][ref]

Getting more specific: 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]

The amount of glycoalkaloids in plants depends also on exposure to light, mechanical damage to the plant, and ripeness or spoiling of the plant. Glycoalkaloids levels are not altered by cooking. [ref]

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 such as pesticides. [ref]

This has led some clinicians to theorize that people who carry genetic variants that significantly reduce BChE function may have food sensitivities for the nightshade vegetables.

Nightshade vegetables are linked to increased joint pain, especially in people with rheumatoid arthritis. [article] Potatoes, especially fried potatoes, are thought to increase the risk of inflammatory bowel diseases due to their glycoalkaloid content.[ref] Additionally, people with psoriasis may be more prone to nightshade sensitivity. A survey from the National Psoriasis Foundation found that eliminating nightshades was beneficial for about half of psoriasis patients who had tried it.[ref]

BChE and Ghrelin:

Recently, researchers have found that there may be another physiological role for BChE in humans. It has been shown that BChE also inactivates ghrelin, the ‘hunger hormone’. Ghrelin is released by the cells of the stomach and causes the stimulation of muscle cells in the stomach that gives us ‘hunger pains’. Ghrelin also activates the brain to cause us to seek out food and is involved in food cravings. Finally, ghrelin is also active in fat storage. [ref]

Both humans and animals with a lack of BChE have higher than normal ghrelin levels. When researchers alter the BChE gene in mice so that they overexpress BChE, the mice have significantly lower ghrelin levels. Researchers have also found that increasing BChE levels keeps formerly obese mice from rebounding and gaining back the weight. [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]

In fact, a recent study in mice looked at a couple of traditional African medicines made from the leaves of plants in the nightshade family. The study found that the leaves of the African eggplant and Black nightshade may help with cognitive impairment in mice.[ref]

The dose makes the poison is a well-known saying, and the right amount of cholinesterase inhibition can be beneficial in specific medical circumstances. (This is definitely not an ‘experiment with this at home’ situation!) 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:

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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. This causes both a decrease in the function of the enzyme and also an alteration to the way that it functions.

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)

Members: Your genotype for rs1799807 is .

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, 30% decrease in BChE, possibly sensitive to nightshades, increased risk of Parkinson’s with organophosphate exposure [ref][ref][ref][ref]

Members: Your genotype for rs1803274 is .

There are other variants in the BChE gene that cause more minor reductions in the enzyme function. These may be more important if combined with the above K-variant or A-variant.

Check your genetic data for rs2668207 (23andMe v4):

  • T/T: typical
  • C/T: slightly lower BChE (4-9% lower) [ref]
  • C/C: lower BChE (>4-9%)

Members: Your genotype for rs2668207 is .

Check your genetic data for rs1126680 (AncestryDNA):

  • C/C: typical
  • C/T: lower BChE activity, increased risk of hyperhidrosis when combined with K-variant
  • T/T:  lower BChE activity, significantly increased risk of hyperhidrosis when combined with K-variant[ref] [ref][ref]

Members: Your genotype for rs1126680 is .

 

These last two are rare mutations, known as F1 and F2, which can cause a delayed recovery from succinylcholine anesthesia.

Check your genetic data for rs28933389 (23andMe v4, v5; AncestryDNA):

  • A/A: increased risk of post-anesthesia (succinylcholine) apnea [ref]
  • A/G: increased risk of post-anesthesia apnea
  • G/G:  typical

Members: Your genotype for rs28933389 is .

Check your genetic data for rs28933390 (23andMe v4, v5; AncestryDNA):

  • A/A:increased risk of post-anesthesia (succinylcholine) apnea [ref][ref]
  • A/C: increased risk of post-anesthesia apnea
  • C/C:  typical

Members: Your genotype for rs28933390 is .


Lifehacks

Everyone should avoid exposure to nerve gas, but anyone with a BChE variant may be even more at risk…  If you’ve been exposed to organophosphates or nerve agents in the first Gulf War, you may be interested in the genetic connections between the BChE variants and Gulf War Syndrome.

Avoiding Organophosphates

Parkinson’s risk is significantly increased in people with the BChE K-variant who are also exposed to organophosphates. This is particularly important for people in agricultural industries. 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 for a few days. See how you feel.  Then eat a potato with the skin on it. Perhaps top it with some salsa with hot chili peppers…

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]

Technical the nightshade family is known as the Solanaceae.

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]


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Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.