Submitted by geistererscheinung t3_1158xwe in askscience
Most of us are aware of the connection between iodine intake and thyroid function. The hormones produced by the thyroid (T3,T4...) contain iodine, which makes the gland unique. But why only the thyroid, or the thyroid at all ? How did iodine-containing thyroid hormones evolve ?
This is a neat answer, but I hope someone will tackle what I think is the most interesting part of OP’s question: why is iodine biochemistry apparently localized in the thyroid? It’s not like we have specific organs for zinc or manganese chemistry. (Or do we?)
What animals have a thyroid? Is iodine chemistry localized in a different organ in the ones that don’t?
It’s precisely because elemental iodine is very reactive. The thyroid has follicles, where iodine is pumped into a gel in ion form, and then enzymatically converted into elemental iodine, where it then attacks thyroglobulin to create thyroid hormones. The final hormones are the only molecules allowed out of the follicular lumen back into the blood.
Elemental iodine? In my thyroid?? Wow, that's really cool. Wikipedia said that the iodation of tyrosine by elemental iodine is a really streamlined process, indicating how T3 and T4 evolved.... Thank you for your answer!
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> > > > > What animals have a thyroid?
Vertebrates. Invertebrate chordates have an organ called the endostyle, which has some functional similarity and is very likely the evolutionary predecessor to the thyroid gland.
> Is iodine chemistry localized in a different organ in the ones that don’t?
Well... many aquatic invertebrates may rely mainly on exogenous thyroid hormones, so they don't need an organ for it. Other invertebrates may have their own endogenous production of thyroid hormones, but without a dedicated organ. Yet other invertebrates, particularly outside the bilaterians, may be less reliant on thyroid hormones in the first place, since they seem to lack an ortholog of the thyroid hormone receptor.
Here is an interesting review article about thyroid hormone signaling in invertebrates.
Thank you for your answer. I'll try to read that article soon. Thyroids are turning out to be really interesting biochemically!
It's really no different from other hormones: they are only synthesized in one organ and then released into the body. Sex hormones are mainly (not exclusively) synthesized in the gonads, etc.
It is fascinating that the body regulates thyroid hormones the same way a chemical plant would regulate a key chemical today. The pituitary gland monitors the level of thyroxine in the blood and emits thyroid stimulating hormone in greater or lesser amounts if the thyroxine level is too low or too high. The thyroid, physically located separate from the pituitary, then produces thyroxine depending on the TSH level it senses. If the sensing function and the synthesis function were physically located at the same place, the body couldn't control what was happening.
Thank you for your answer. Kinda cool how isolated the thyroid is...yet how tightly controlled the process must be.
Thank you for emphasizing that. Localization was my original question, and I added the others for support.
Just about all hormones are made and stored in their own glands and released carefully in response to circulating chemical signals. One really unpleasant symptom cluster from cancers of hormone producing glands is indiscriminate outpouring of hormones by the now unregulated cancerous cells which are still well organized enough to produce hormones unchecked. This can happen with the thyroid, adrenals, pituitary, etc.
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The majority is stored in the thyroid, but it’s also stored in the breasts, prostate, rectum, and many other places as well.
An answer with a citation, nice!
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Cell signaling is so interesting, thanks
I can't read the citation now, but the thyroid hormones affect mitochondrion function, so iodine was key to the metabolism of mitochondria.
Thyroid hormones affect regulation of mitochondria and their metabolism, but through signaling. Iodine isn't directly part of metabolism. That may have been what you meant, just wanted to be clear.
Plus it is commonly found in seawater. So if life evolved in seawater it would use elements available to it.
How did people far from the ocean survive back in the day? If they couldn’t access iodized salt or anything else from the ocean?
Other animals are a good source!
Meat, eggs, and dairy all are good sources of iodine- and some organs especially liver. Apparently 1300 years ago someone in China had already figured out you could treat goiter by giving the patient ground up animal thyroid gland. Pretty cool.
https://en.wikipedia.org/wiki/Goitre#History
Also apparently in more iodine-rich soil, plants uptake enough to also be a good source, probably where the animals at lower trophic levels are getting it.
Does this indicate that the thyroid itself (or what will become the thyroid) goes back to the earliest days of our biological ancestors?
Does all life get iodine through other iodine containing organisms? Or do some get it through natural sources, like iodised salt (assuming that it occurs naturally).
It would he interesting it f it’s something that just got perpetually recycled since the dawn of life.
I know this answer: It's far more prevalent in the sea than anywhere else, and diminishes in concentration as you move inland. Many inland regions, especially mountainous regions were traditionally so deficient in iodine that many people suffered from extreme deficiency.
https://en.wikipedia.org/wiki/Congenital_iodine_deficiency_syndrome
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> It’s a bit of a mystery.
But
> The reason why iodine was used, is that molecules that contain iodine are highly reactive and often powerful antioxidants,
So, it’s not a mystery? Or just not a mystery why it was originally used, but rather how it was retained?
I don’t have anything to add to this. But wow. I hope to be as knowledgeable in a topic as you are one day. Very well put (granted I don’t really understand a lot of the technical terms). But yea man, keep it up!
Thank you for your response. I'll try to look over that article. The reactivity/antioxidant part is especially interesting.
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Iodine is in seawater so was part of the environment of early life. This meant that evolution incorporated it into its core chemistry - it was always around. As animals arose on land some areas were iodine deficient but the element was firmly in biology by then
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Does that mean that we, by the same token, are one retrovirus away from going back to egg-laying ?
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Ok, really hope that doesn't happen. Let's let sleeping dogs lie.
To add to this, it’s also why you’re mostly likely to find halogen-containing biomolecules in aquatic species, especially marine mollusks. The dye Tyrian purple would be a classic example.
It's wild to me that that molecule and it's derivatives are so localized to certain species. For folks information, Tyrian purple is indigo that has been substituted on both ends with bromine groups (6,6'-dibromoindigo). Indigo itself is only found in a couple species (indigo and woad are the most prevalent). Also Tyrian purple was harvested by "milking" a certain snail for minute amounts of the dye.
I went to a farm near me to buy some madder (the roots of which contains the anthraquinoidal dye alizarin) and one of the farmers, an older man, told me all of that above and I asked him if he was a chemist? Non chemists don't use words like "substituents."
"In a past life," he said.
I use Dulse flakes ( dried seaweed ) daily to get my dose of iodine. It's loaded with the stuff.
Im a bit shocked your normal diet doesn’t provide you with enough iodine. Are you on some crazy restrictive diet?
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Iodine deficiency of some kind isn’t all that rare actually - even in the first world. Severe iodine deficiency used to be very common in the Midwest, with supplementation in salt increasing IQ in the region by double digits. 70% of UK people tested in a 2011 study were iodine deficient. It remains one of the most common micronutrient deficiencies worldwide.
https://en.m.wikipedia.org/wiki/Iodine_deficiency
I kind of worry about it coming back, as restaurant, fast food and processed food is commonly not using iodized salt, and at home ‘sea salt’ that hasn’t been iodized is trendy. Dairy is another important source of iodine but processing facility changes have reduced milk content. This opens the door to more regional or sub population deficiency
Do those have less oil than the seaweed sheets? So many seaweed sheets are covered in sunflower oil which I’m allergic to.
The only ingredient is dried organic Dulse. I sprinkle one teaspoon a day on my lunch, that's all you need.
Thank you, I will look out for it!!
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Others have made good points about halogen availability in marine life, but I think it's also good to look at it from a biochem perspective. T3 and T4 use phenol rings with iodine substituents sticking off them. The size of these groups will be pretty fuggen big compared to organic groups with similar functions. This makes sense, because thyroid hormones have a direct effect on the overall pace of metabolism across the whole organism. You want that lock to turn with a big key, so that it won't easily get accidentally triggered. Put another way: the harder it is to accidentally trigger thyroid hormone receptors, the better an organism will be at autoregulating its metabolism.
Why not use a big ol' peptide like insulin ? In any case, that's an interesting observation -- you gotta make your metabolic signaling unambiguous.
That's another good question, which again deals with unambiguous signaling. Remember that molecules have not only size in space, but also a shape and a pattern of electron density. So, yes, you could make a protein as big or bigger than T3, but will it fit into the necessary active site the same way? And will it electronically interact with the active site the same way?
For peptides, the bond angles of the main chain are given by something called a Ramachandran Plot, which works out the most likely shapes a peptide bond can form in space. In this case, maybe you could have a protein with a pair of tyrosines that could meet up and maybe look kind of like T3? Well, the necessary bond angles make that unlikely, so such a shape would not persist in space for enough time to matter. Even if it did, you'd have the rest of the protein hanging out at weird angles, preventing a good fit with the intended receptor.
Finally, even if all that worked, there's still some intentional interaction with the iodine substituents necessary to induce a tight fit. You could get a couple tyrosines in there to fake the rough shape, but how are you going to get protein parts in there to fake the iodine interactions? There's no way. (A) nothing else is even kind of shaped like those iodine substituents, and (B) even if there were, you couldn't stick them into that binding site without popping the whole protein out. Thus, the iodine groups help ensure that only T3 will reliably fit into the intended receptor site.
Okay, that's a very clear answer. And it seems, at least from Wikipedia, that tyrosine and iodine are a good combo because the iodation reaction with elemental iodine is pretty consistent and doesn't really need a enzyme... right? I could be totally wrong. Thank you for your time!
Phenyl rings and iodine go together like peanut butter and jelly, for reasons outside the scope of the question. For thyroid hormones though, an enzyme is used called thyroperoxidase which handles both the management of iodine's oxidation state, and its addition to tyrosine residues.
Its just one of the trace elements (among cobalt, copper, zinc, chromium, flouride etc for various other specialised mechanisms) that the life forms on earth have evolved to utilise for specific purposes. Its very hard to 'exactly' trace back the evolutionary mechanisms for specific metabolic pathways in highly evolved creatures and be sure that a particular narrative is the only one.
I know it kinda doesn't answer you question exactly. Life just used and incorporated whatever chemicals (in roughly the same proportion) were available in the environment around them.
Thank you for your answer!
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Bbrhuft t1_j91bx8b wrote
It's a bit of a mystery. However, the evolutionarily roots of iodine cell signalling is very acient, almost all all multicellular life uses iodine containing molecules, including plants.
A recent interesting hypothesis proposed that... Given that almost all multicellular life uses iodine containing cell signalling molecules, they must have evolved very early billions of years ago in early single celled organisms, and the development of multicellularity and iodine containing cell signalling molecules went hand in hand.
The reason why iodine was used, is that molecules that contain iodine are highly reactive and often powerful antioxidants, they are very useful.
Crockford, S.J., 2009. Evolutionary roots of iodine and thyroid hormones in cell–cell signaling. Integrative and comparative biology, 49(2), pp.155-166.