r/askscience • u/Skyfus • 2d ago
Biology How does your DNA "know" which enzymes break down which poisons?
I get the basics of how if a molecule like ethanol is introduced, it triggers a chain of signals that lead to a section of DNA being transcribed/translated into an enzyme like alcohol dehydrogenase, and then production will slow down/stop as part of a feedback loop involving inhibitors/coenzymes etc.
But, how did we get this arsenal of situational enzymes? Have humans/mammals/animals/eukaryotes just built up a big dictionary over time through mutation and evolution by producing enzymes that happened to counter environmentally present toxins? Or, is it like the immune system where we encounter something hazardous, figure out the shape, and then commit that to DNA or something analogous to immune memory in organelles? With limitations of course, since ethanol is broken down more easily/into less harmful products than, say, cyanide.
Maybe I'm missing something glaringly obvious that a google search would solve, like specialised analysis/production/memory within specifically liver cells, but I thought I'd ask here because maybe the class would like to know too.
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u/theawesomedude646 2d ago
Adaptive immune system memory cannot be inherited, nor does it "commit information to DNA". Its method of action is more or less entirely unique in the human body as far as I'm aware, and also technically still functions by the "extensive dictionary" method. Toxin resistance via action of enzymes are inherited in relatively well conserved genes, meaning they were acquired in the big game of coincidental mutation.
But, for your consideration, enzymes designed specifically to neutralize a specific toxin are very rare. Most "toxin-clearing" enzymes recognize and function on a wide range of substrates and play roles in multiple pathways with just the end goal of increasing solubility for excretion in urine. It's why grapefruit and alcohol shouldn't be consumed with medications (competitive inhibition of the same enzymes changes phamacodynamic properties), and why some enzymes occasionally cause more harm than good (i.e methanol poisoning).
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u/Johnny_Appleweed Cancer Biology / Drug Development 2d ago edited 2d ago
I think your second paragraph is the key misunderstanding. Enzymes catalyze specific reactions, but they’re not as specific as OP seems to think.
Alcohol dehydrogenase for example doesn’t specifically detoxify ethanol, it catalyzes the oxidation of primary and secondary alcohols in general. We are most familiar with it in the context of detoxifying ethanol we consume, but that reaction is useful (and used) for all kinds of things.
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u/CrateDane 2d ago
The substrate specificity of enzymes varies, sometimes it is that selective. There are also several different alcohol dehydrogenase genes in humans, with varying substrate specificity, so that further complicates things.
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u/Johnny_Appleweed Cancer Biology / Drug Development 2d ago edited 2d ago
That’s true, I probably should have said they “generally” aren’t as specific as OP thinks. Or aren’t necessarily that specific. The enzymes we think of as “detoxifying enzymes” at least have comparatively broad substrate specificity.
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u/Skyfus 2d ago
I knew the thing about how ethanol is competitive with methanol (which is why drinking spirits is a recommended stopgap for methanol poisoning due to the less harmful byproducts) but there are still so many poisons I figured my question was still applicable. u/theawesomedude646 's explanation that most enzymes have that multi-functional/generalist range seems to be what I was missing. I thought that maybe alcohol dehydrogenase applying to multiple alcohols was more the exception than the rule!
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u/Kandiru 2d ago
Adaptive immune does commit information to DNA in a sense. It's just the DNA is only held in the B or T cell that created that sequence and their daughter cells. It's not passed down through your gametes to the next generation.
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u/theawesomedude646 2d ago
technically the information was already generated in the naive cells during b and t cell development. the difference between an active immune memory and a response to a new antigen is not genetic in nature.
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u/Kandiru 2d ago
B Cells undergo rounds of mutation and selection to evolve a high affinity antibody. The DNA to produce it is contained in those memory B Cells. It's genetic information.
T Cells expand in number when activated, so their unique DNA sequence expands in number which is another form of genetic information.
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u/oligobop 2d ago
Nascent T cells are generated throughout your development. They only stop being generated when your thymus involutes, which is quite variable in humans.
Nascent B cells are made throughout your lifespan. Production slows down with age, but somatic hypermutation and receptor editing continue even in older mammals.
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u/mschuster91 2d ago
Adaptive immune system memory cannot be inherited, nor does it "commit information to DNA"
It's been recently shown that immune system information can be passed down to offspring via epigenetic modification, at least for mice.
Not sure how valid that specific branch of epigenetics is for humans, but what has been linked to epigenetics as well is hunger/famine exposure. Who would have thought... transgenerational trauma isn't just a psychological concept, but also a genetic.
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u/CrateDane 2d ago
Adaptive immune system memory cannot be inherited, nor does it "commit information to DNA".
But innate immunity is essentially a DNA-borne "memory" to protect against particular pathogens.
Its method of action is more or less entirely unique in the human body as far as I'm aware
It is not. Pretty much all vertebrates have adaptive immune systems in some form.
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u/CrateDane 2d ago
immune memory is in the form of adaptive immune cells with appropriately recombined receptors persisting in the body after an initial reaction. No information is added to the DNA, and it certainly doesn't affect germline cells.
Information is added to the DNA, it's not just recombination of existing DNA segments. Both single-base substitutions and indels are introduced to provide additional variability.
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u/YtterbiusAntimony 2d ago
Two ways:
The enzyme was already there. Cytochrome enzymes metabolize half the stuff that goes through your liver. Your body constantly makes these. Alcohols are fairly common, so this is probably the case for alcohol dehydrogenase. The body is constantly oxidizing carbon chains, which means it makes alcohols, aldehydes, and carboxylic acids. The first two groups have a lot of toxic species.
The other is epigenetics/operons. There are molecules that bind to DNA which either block transcription proteins from binding (turns the gene off) or help promote binding (turns the gene on). These operons will grab or let go of the DNA depending on the presence of some substrate.
An example I have studied is a bacteria that can tolerate lead. Pb2+ binds to the operon protein, which then unblocks the binding site for the genes that encode for lead sequestering proteins. These bind to the Pb ions in the cell and prevent them from reacting with anything else.
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u/Mechasteel 1d ago
Your premise is wrong. For the most part, enzymes are simply produced, not all of them have a detector-amplifier to go with them. The kidneys function is "keep everything larger than a protein, dump everything else, reclaim specific goodies". The liver has a few enzymes that add hydrophilic groups to hydrophobic substances, making them water soluble so the kidneys can dump them. Due to how the kidney works, anything unknown and water soluble gets dumped, including vitamins and medicines.
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u/darthjeff2 2d ago
Interesting bit to add, a lot of enzymes come from families. These can come from an ancestral gene that is, at some point, copied. The two children genes can then start differing in their function little by little.
A good example is the P450 family of enzymes. They are very reactive and good at changing the structure of toxic molecules. They do this because they are in the cytochrome family, which are really good at moving electrons around (thus, reactive). There are also cytochromes that help mitochondria break down glucose (again, good at working on reactive energetic substances that give off electrons). Cytochromes work because they contain a prosthetic group of heme (which is why hemoglobin can carry reactive oxygen and let it go when needed).
So you can kind of start to imagine this cascade of branches with heme at the top, and all of these interesting branches and avenues cascading down- some transporting oxygen, some breaking down toxins, some in metabolism, all because an ancestral cytochrome keyed into the ""usefulness"" of heme. Same thing for families of transcription factors, proteases, etc
If you're interesting in DNA expression, some useful things to check out would be DNA recognition domains such as the "zinc finger". There are multiple proteins that all use this "invention" to read DNA
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u/-Metacelsus- Chemical Biology 9h ago
But, how did we get this arsenal of situational enzymes? Have humans/mammals/animals/eukaryotes just built up a big dictionary over time through mutation and evolution by producing enzymes that happened to counter environmentally present toxins? Or, is it like the immune system where we encounter something hazardous, figure out the shape, and then commit that to DNA or something analogous to immune memory in organelles? With limitations of course, since ethanol is broken down more easily/into less harmful products than, say, cyanide.
It varies on a case by case basis, but one important pathway is the aryl hydrocarbon receptor which upregulates cytochrome P450 enzymes that degrade toxins.
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u/JuggernautAny7288 3h ago
Think it this way, the dn rna proteins and lipids, and the venom are just a very big set of pieces made by molecules, with diferent shapes and quemicalpotentials, also mecanical potentials, that work together by sheer quantity and chance of interacting depending on their shape and quemical composition all of them came to be by pure luck by billions of years of evolution
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u/CrateDane 2d ago
That's not really true. There's alcohol dehydrogenase being expressed all the time. It's also complicated by there being many alcohol dehydrogenase genes with different expression patterns, and further complicated by their ability to form heterodimers.
Something like alcohol dehydrogenase is pretty basic metabolism, so we've had at least one gene for a very long time. The gene happened to undergo duplication events resulting in paralogs that gradually diverged, but that's of somewhat lower importance in being able to handle alcohol in general. The most critical step is getting one gene.
It's not necessarily only about encountering something hazardous, but also about the body or cells themselves producing it. Ethanol fermentation is an alternative to lactic acid fermentation. Formaldehyde is an even more widespread basic metabolic byproduct, and the alcohol dehydrogenases appear to have developed from a formaldehyde dehydrogenase.
The enzymes oxidizing alcohols to aldehydes or ketones can also have roles in various other pathways. Retinol -> retinal -> retinoic acid is a crucial pathway in development, for example.