Human health, for better or worse, is not immune to trends and fashions. 200 years ago, leeches were popular among doctors.
Now, the concern for detoxifying the human body through metabolic pathways and the involved genes seems to be gaining strength.
Detoxification is, by definition, the process that the organism performs to eliminate toxic substances, both those that have been incorporated from the environment and those it has produced naturally by itself.
The first thing to understand is that it is a process the body performs naturally on its own. Because if it didn’t, you would die.
It is considered that there are three general steps to carry out the process, although they depend on the specific toxin to be eliminated.
Step 1 is the direct modification of the toxin to try to neutralize it or make it less dangerous.
Step 2 is its conjugation with elements that make it more soluble in water. Besides facilitating its transport through the organism, it aids in its excretion in urine and/or feces.
Step 3, when it meets these conditions, is to transport it to an organ that can expel it to the external environment.
Usually, for excretion to the exterior, it is transported to the kidneys or intestines, although some molecules can be partially eliminated by the lungs. For example, a small part of the alcohol we ingest is expelled through respiration.
The Complexity of Detoxification
For steps 1 and 2, the organ with the greatest responsibility as the body’s purifier is the liver. That is precisely why alcoholics have liver damage: because it is the tissue that is responsible for eliminating alcohol.
Yes, alcohol is toxic, there are no surprises here. Why did you think you turned red when drinking? From an excess of essential nutrients?
Doing all this work requires a real arsenal of different enzymes.
For step 1, the famous cytochrome P450 dominates. P450 is actually a superfamily of hemoproteins (proteins with a heme group containing iron; hemoglobin is an example of a hemoprotein) with the ability to interact with a wide range of compounds.
Its activity is mainly oxidative (loss of electrons), although they also have reductive (gain of electrons) and hydrolytic (breaking bonds by adding water molecules) capabilities. The idea is to neutralize the toxic molecule in any way possible.
In humans, P450 encompasses 57 genes and more than 50 pseudogenes. This superfamily metabolizes approximately 80% of all currently used medications.
That is why the effectiveness and duration of a drug in the body are related to the state of the treated person’s liver.
For phase 2, the enzymes and genes involved are more diverse. If the liver considers that adding X molecule achieves the goal, it adds it. Need sulfur? We got it. Lacking acetyl or methyl groups? We have them. Can we add an entire amino acid? Go ahead. There is no poverty in the liver.
Discussing all the detoxification processes of the body would require an entire blog just for them, so we prefer to focus on the so-called “Methylation Detoxification Cycle,” which has recently gained strength as a methylation detoxification.
Methylation Detoxification Cycle
This cycle would participate in phase 2 and is the process in which methyl groups formed by one carbon and three hydrogens (CH3) are added. The main donor of methyl groups in these reactions is the amino acid methionine.
Therefore, the methylation cycle and its detoxifying effectiveness depend on the reserves of methionine and homocysteine.
Why homocysteine? Because this amino acid (yes, another amino acid) allows the regeneration of methionine. If you have read about vitamins B6, B12, and folic acid in these pathways, it is because they are necessary as cofactors and/or regulators of the process. The important thing is to keep methionine levels high, as it is the methyl donor.
In fact, excess homocysteine, on the other hand, IS BAD. Elevated levels often serve as an indicator of failures in the methylation cycle, indicating that the conversion to methionine is not working.
On the genetic side, there are a series of genes studied in the cycle. Don’t worry, we will limit formulas and long names to a minimum. We are not a biochemistry blog.
- MTHFR. The MTHFR gene converts 510-methylenetetrahydrofolate to 5-methyltetrahydrofolate (levomefolic acid). For most, this is the same as saying nothing. In this reaction, what matters is levomefolic acid, the main active form of folic acid (this one might sound more familiar). This compound is necessary for DNA replication and the cysteine and homocysteine cycles, making this gene a key regulator of the methionine and folate cycles. Some professionals consider the MTHFR gene one of the main detoxifying genes on a particular detoxification gene scale. Even adding diets designed for the MTHFR enzyme. In that regard, we will not comment because we are not experts in these biochemical pathways.
- COMT. The COMT gene catalyzes O-methylation reactions, and its main function is to inactivate catecholamines (hormones produced by glands on top of the kidneys). And what does that have to do with us? In short, the methyl group it uses comes from methionine. Methionine converts to a form called SAM, and COMT removes the methyl group. If you don’t have methionine, this enzyme’s main utility is boredom. If that didn’t make it important enough, it can interact with multiple drugs, either indirectly because they also act on catecholamine pathways or directly on the drugs themselves, like morphine or mirtazapine.
- AHCY. Remember we said COMT removes a methyl group from SAM? Sounds like the beginning of a bad comedy. Well, the AHCY gene codes for an enzyme that takes what is left and produces homocysteine. Basically, AHCY converts methyl-less SAM into homocysteine. That’s why it’s another regulator of methylation.
- MTR and MTRR. Here we have two genes, MTR and MTRR. As you might guess from those two names that sound like they come from twins in an unoriginal family, their functions are closely related. The MTR enzyme adds a methyl group back to homocysteine, regenerating methionine. It is the key enzyme for producing methionine, so it is also called methionine synthase. On the other hand, the MTRR enzyme’s function is to keep the MTR gene active. It’s its support to keep it working; if it fails, the methionine cycle is interrupted.
Answering the question you all might have at this moment: it is called O-methylation because they attach the methyl group to an oxygen. It’s beautiful when names make sense.
One piece of advice we want to give you: don’t take for granted the products sold as detoxifiers. Like any good trend, there are individuals who may want to exploit it to make money.
Ask and read about these products, supplements, or dietary changes, especially if you have special conditions and pathologies. Even vitamins in excess are harmful, with damage ironically often occurring in the liver itself.
With tellmeGen’s Advanced kit, you will know what genetic variants you have of several of the genes mentioned in this blog. We always recommend that before taking action, you consult with other professionals to act with knowledge. Take care.
