Phase II Detox – NATs

N-acetyltransferase is a phase II detoxification enzyme that helps to metabolize aromatic amines, drugs, cigarette smoke, and carcinogens. Basically, it makes specific toxins more water soluble so that they can be excreted through a process called acetylation.

There are several common genetic variants that can classify a person as a slow, intermediate, or rapid acetylator. The rapid acetylator is considered to be the ancestral type and is the most common type in Asian and African populations; Caucasian people are actually slightly more likely to be intermediate or slow acetylators.[ref]

Historically, N-acetyltransferase was first recognized in the 1950s to play a role in the metabolism of tuberculosis drug. A significant percentage of people were found to be poor acetylators resulting in significant side effects of the tuberculosis drug, isoniazid.

Genetic variants involved:

NAT1 metabolizes p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS).[ref] PABA used to be commonly found in sunscreens, and PAS is used as an antibiotic for tuberculosis. It also breaks down components of cigarette smoke and heterocyclic aromatic amines, which forms when meats and seafood are grilled at high temperatures.

There have been studies linking NAT1 genetic variants to an increased risk of bladder, colon, breast, lung, prostate, and pancreatic cancers. [ref]

Smoking is even more risky for those with NAT1 slow acetylator variants. NAT1 slow and intermediate acetylators had been shown to have a significantly higher risk for esophageal cancer and lung cancer in smokers.[ref]

It has recently been found that NAT1 slow acetylators have more DNA adducts formed with heterocyclic aromatic amines (carcinogens from meat being cooked at high temps). [ref]  Another study also found red meat consumption for slow and intermediate acetylators to be linked to esophageal cancer. [ref]

NAT1 is also involved in folate metabolism and folate may be a co-enzyme for NAT1 hydrolysis of acetyl-Coenzyme A [ref].  Rs15561 -A/A (below) has been associated with cleft lip (especially if the mother smokes) and spina bifida. Note that it is the baby’s genotype, not the mother’s, that is being studied, so this is another really good reason not to smoke. [ref] Both of those conditions are linked to folate metabolism and the methylation cycle.

Check your 23andMe results for rs4986782:

  • A/A: NAT1*14B, slow acetylator [ref]
  • A/G: slow acetylator,
  • G/G: normal

 

Check your 23andMe results for rs15561:

  • A/A: reduced function [ref]
  • A/C: reduced function
  • C/C: normal

 

Check your 23andMe results for rs6586714:

  • A/A: lower risk of colon cancer from cooked meat carcinogens (protective) [ref]
  • A/G: lower risk of colon cancer from a cooked meat carcinogens
  • G/G: wildtype/common

There are several other SNPs that are not included in 23andMe data so the above SNPs are not the complete picture for NAT1.

NAT2 also catalyzes the acetylation of a couple of types of carcinogens (aromatic and heterocyclic amines) which include tobacco smoke, well-cooked meat, and exhaust fumes. NAT2 is found mainly in the liver, in contrast with NAT1, which is found throughout the body. NAT2 has been studied extensively and is thought to play a role in the risk for several types of cancers.

NAT2 polymorphisms also create rapid, intermediate, and slow acetylators. Slow acetylators don’t clear out toxins as well and are at a somewhat higher risk for bladder, lung, breast, and esophageal cancers. Rapid acetylators can actually make some toxins more reactive and may be at a slightly higher risk for colon cancer.

There is an online tool from the University of Albany to determine your NAT2 phenotype.  http://nat2pred.rit.albany.edu/  You will need to look up your data for six different SNPs.   It asks you to put in your NAT2 alleles for the following:

NAT2 rs1208 – A, has also been found to be involved in increased insulin resistance, although, to me, the effect looked pretty small.  [ref]

NAT2 is also being studied in relation to bacteria which can produce it, and their relationship to drug metabolism.


Lifehacks

If you need another reason not to smoke, being a slow or intermediate acetylator is a really good reason to never pick up a cigarette.

Slow acetylators may want to cut back on fried meats to limit the intake of heterocyclic aromatic amines.

Further reading:

Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery

5 Comments on “Phase II Detox – NATs

  1. I have red +/+ for nat2 r197q. Having a hard time figuring out what this means.

    • Hi Denise,
      A little bit of poking around shows that NAT2 R197Q is also known as G590A or rs1799930. Above in the section on NAT2, you’ll see that those are part of how your NAT2 acetylator status is determined in the tool that I linked to. If you are homozygous for R197Q, you are very likely to be a slow acetylator for NAT2. This would mean that you don’t process the carcinogens in cigarette smoke, burnt foods, or smog very well.
      Debbie

      • Thank you so much Debbie! I will take it from there. I really appreciate you taking the time to respond. Your site is wonderful.
        D

  2. What would GG alleles on rs1208 and CC on rs1801280 mean, particularly regarding detoxing from heavy metals, vaccines, ect?

    • Hi Stephanie,

      The rs1208 GG genotype and the rs1801280 CC genotype are part of the picture for slow acetylation. In general, you need to plug in your genotype for all of the listed alleles into the NAT2 predictor at the Univ. of Albany (link above) to get a full picture of whether you are a slow or fast acetylator.

      NAT2 is important in getting rid of the carcinogens from cigarette smoke and smog — and in metabolizing a couple of different types of medications. I can’t find any research or anything that indicates that it would be important in heavy metals or vaccines.
      Hope this helps,
      Debbie

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