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The thyroid hormone converting enzyme human deiodinase 1 is inhibited by gold ions from inorganic salts, organic substances, ...

helvella profile image
helvellaAdministrator
11 Replies

All that glisters…

Not in the least clear whether this is likely to be of interest or significance to anyone. But I do think that the impact of anything on thyroid-related enzymes is an important avenue.

Chem Biol Interact

. 2021 Oct 15;109709.

doi: 10.1016/j.cbi.2021.109709. Online ahead of print.

The thyroid hormone converting enzyme human deiodinase 1 is inhibited by gold ions from inorganic salts, organic substances, and by small-size nanoparticles

Andreas Georg Weber 1 , Barbara Birk 2 , Chantal Müller 3 , Steffen Schneider 4 , Bennard van Ravenzwaay 5 , Dorothee Funk-Weyer 6 , Robert Landsiedel 7

• PMID: 34662569

• DOI: 10.1016/j.cbi.2021.109709

Abstract

The selenocysteine-containing enzyme class deiodinases (DIO) consists of three isoforms. DIOs play a role in regulation of thyroid hormone (TH) signaling through the removal of iodide from TH leading to TH that interact with the hypothalamic-pituitary-thyroid (HPT) axis with differing potency. Some gold-containing organic substances are known to inhibit many selenoenzymes, including DIOs. It is, however, unclear whether the Au-containing substances or the Au ions are causing the inhibition. In this study, five organic and inorganic gold substances as well as three gold nanoparticles (AuNPs) were tested for their potential to inhibit DIO1. The enzyme activity was tested using human liver microsomes as an enzyme source and reverse T3 as a substrate; iodide release was measured by the Sandell-Kolthoff method. The three organic gold substances aurothioglucose, auranofin and sodium aurothiomalate inhibited DIO1 with IC50 between 0.38 and 0.75 μM while their structural analogues lacking the gold ion did not. Likewise, the two tested gold salts, Au(I) and Au(III) chloride, showed a concentration-dependent inhibition of the DIO1 with IC50 values of 0.95 and 0.57 μM. Further, AuNPs of different sizes (100, 30 and 5 nm diameter) were tested with only the 5 nm AuNPs leading to inhibition with an IC50 of 8 × 1014 AuNP/L. This inhibition was not caused by the Au ions released by the AuNP into the incubation media. The exact mechanism of inhibition of DIO1 by 5 nm AuNPs should be further examined. In conclusion, the microsomal DIO1 assay demonstrated the inhibition of DIO1 by gold ions originating from different gold-containing substances, but not by Au released from AuNPs; rather DIO1 is inhibited by 5 nm, but not larger, AuNPs.

Keywords: Deiodinase; Enzyme inhibition; Gold; Microsomes; Nanoparticles; Sandell-Kolthoff.

pubmed.ncbi.nlm.nih.gov/346...

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BB001 profile image
BB001

Is anyone able to interpret this and give me the bottom line? I gather gold containing substances inhibit Dio1 enzyme in some way that needs investigating. However what's important to me, is what can I do about it? I know I'm homozygous with genetic mutations on Dio1 so anything I can do to make Dio1 work better is good.

helvella profile image
helvellaAdministrator in reply toBB001

Are you exposed to gold nano-particles? If not, probably nothing to worry about and nothing needs to be done.

It was primarily to highlight that something, even if only a single thing in the entire universe, can affect our conversions by affecting the DIO1 enzyme. I can't remember anything else like this - other than not having sufficient selenium to make the enzyme in the first place.

I am not aware of anything that boosts deiodinase enzyme activity.

gabkad profile image
gabkad

In the far reaches of my memory there's something about gold treatment for arthritis.So I googled it. Gold salts may be used for rheumatoid arthritis. I don't know anything about which types. I don't know how frequently they are used.

oral capsules: auranofin (brand name: Ridaura)

helvella profile image
helvellaAdministrator in reply togabkad

Yes - it is.

This is a link to some papaers on the uses of gold - specifically says nanoparticles which are, it seems, the problem posted about:

sciencedirect.com/topics/me...

gabkad profile image
gabkad

Bonus (not)An oral gold formulation, auranofin (Ridaura), was approved by the Food and Drug Administration in 1985 for patients with RA. The drug never became popular, though. That was in part because of adverse reactions such as blood disorders, rash, digestive upset, kidney and liver damage.

helvella profile image
helvellaAdministrator in reply togabkad

I hate the term "popular" being used for medicines. Pop tunes - fine. Things that might make you better - does it bear any similarity to weekly sales charts of records (or downloads)?

BB001 profile image
BB001

So, do we get nanoparticles from having gold crowns fitted? I've got a gold crown on top of a root filling. There is an infection at the bottom of the tooth and the dentist needs to drill the crown and amalgam filling to get to the infection to treat it. None of this sounds good. Did the researchers give any idea how long the interference by gold on the Dio1 enzymes lasts?

helvella profile image
helvellaAdministrator in reply toBB001

That is way too detailed - you need to talk to your dentist. There are various gold-based substances used in some dentistry and I'd have no idea whether any might have been used on you.

But fragments of gold are not the issue.

gabkad profile image
gabkad in reply tohelvella

Gold from a crown is elemental and not ionic. The reason for using gold is because it's the least reactive metal. Stainless steel is also non reactive but it can't be made with lost wax casting technique so accuracy is non-existent. Gold crowns are still made by hand.

I have two so far and will be replacing a couple of tooth coloured fillings. These things are leaching chemicals. My gold crown was less expensive than a ceramic crown. And I hope

it's the last time these teeth are bothered. I can't say the same for these lousy tooth

coloured fillings. They chip, they wear away, I get food stuck all the time. Last time, I piece of the filling came off but got stuck in the gum tissue. Felt great.

😡😱

BB001 profile image
BB001 in reply togabkad

Thank you for the clarification. I hope your teeth get sorted OK.

gabkad profile image
gabkad in reply toBB001

When the budget allows. The C situation gutted my income. Maybe early next year.Initially my dentist thought I was a bit bonkers because I wanted gold but then she

realized removing the filling and replacing it would just end up with the same problem again. I like my bling. It's a back tooth. Over the next couple of years I'll get all the fillings changed in my back teeth because even chewing gum gets stuck on these things.

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