Talk:Histamine N-methyltransferase

A quick review - looked at the old GA feedback.
@Maxim Masiutin

The GA feedback - not sure every point was covered nor if every point was ever super relevant - against the GA guidance.


 * 1) There is a section in here that explains how information from a gene becomes a protein. I know I often comment about target audience, but in this case I think it is rational to point to the WP article that talks to this really major subject - Gene expression I could see some light preamble but the topic is about the protein and this description of GE takes up discussion space - one has to assume the reader has some base knowledge.
 * 2) I think some of the language might be in parts very clunky - entering the bloodstream and such. I am happy to take a run at some of this - but likely later in the week.
 * 3) I thought the structure of the steroid-21-hydroxylase article was really better - building from an expanded lede - gene - to protein - to actual enzymology dialog - role in pathologies (if any) - history of discovery - as we talked about - I think the target audience should be a UK A level Biology student - what they are exposed to is online.
 * 4) I did not check the references - but looking at https://www.uniprot.org/uniprotkb/P50135/entry it looks fairly accurate.
 * 5) Again seeing this as a unique protein - should be lots of data on how one describes a protein.
 * 6) The enzymology part can get deep - and kinetics, active sites, substrate binding, I think it is easy to get trapped in CLOP - reflecting on this, I almost think making the discussion shallow has merits, again the S21H article was fairly good as to general balance - I think this one swings the other way.
 * 7) Not sure if this helps - but I would not re-submit yet, there are some typos and spacing issues also.

Dr. BeingObjective (talk) 01:06, 28 November 2023 (UTC)


 * Yes, thank you! I will not resubmit yet. There is a schematic still missing.
 * As for the lead, I did not write it until we complete the body.
 * The lead should be based on the body, so I left it for later.
 * Let me think hot to link to the Gene expression better.
 * Should I have some other ideas or find typos, I will find them.
 * Should you also notice something or have ideas, please contribute.
 * Thank you! Maxim Masiutin (talk) 01:32, 28 November 2023 (UTC)
 * Not a problem - I'll take a look in the morning.
 * BeingObjective (talk) 01:37, 28 November 2023 (UTC)
 * I have resolved all the issues described by the reviewer and that you raised here, thank you very much! I resubmitted the article for the GA review. Maxim Masiutin (talk) 01:21, 30 November 2023 (UTC)

General Flow etc. Seeking to understand - so I can add value.
@ Maxim Masiutin

I looked at the structure of the S21H article, I understood this likely follows a prescribed format? Perhaps I am mistaken - logically, I can see a flow that would be.

'''Lede/Overview - I think it is LEDE oddly -- Gene -- Protein -- Activity -- Pathologies -- History -- etc. I think the species/distribution are oddly placed -- IMHO -- the function/mechanism - is low in the article - clinical sig. -- but if this maps to some guidance - I understand it is a requirement. '''

I noted a lot of data in the infobox structure - I assume it is a template - and I stated - my molecular biology skills are like a decade or more out of date.

It might seem irrelevant but left to my own professional devices - I'd likely have gone for:

'''Lede/Summary -- History -- Gene Info. -- Protein Data -- Chemical Functionality/mechanism -- Distribution -- Clinical Sig.'''

About the degree of detail and target audience:


 * 1) Gene Info/gene expression - mixed feelings - S21H has no deep discussion on gene expression and I think any attempt to really expand this might make this article not align with other similar articles in WP - as mentioned - pointing to a fairly elaborate description article is good enough. So deleting out the current explanation - makes sense - I was going to do this - but wanted to ensure you are in agreement.
 * 2) The functionality/mechanism and equations - this is where I wonder who this is again targeted to - it is very detailed in S21H - I think this can be simplified  - this is really fairly detailed.
 * 3) There is a very good article - Methyltransferase. I think your opening likely will be 'Histamine N-methyltransferase (HNMT; Molecular Interaction Map #  605238) is a cytoplasmic protein that belongs to the methyltransferase superfamily and is one of two enzymes involved in the metabolism of HA....'

Just a few late night mumblings - BeingObjective (talk) 07:22, 28 November 2023 (UTC)


 * We cannot change the order of the sections much in the article on 21-Hydroxylase and on Histamine N-methyltransferase. Although we can move between certain sections, we cannot put the History section to the beginning. Whereas articles in peer-reviewed journals usually start with the History, in Wikipedia, History is among the last sections. Probably, this is because in Wikipedia, there is a rule that the most important information should come first; I don't know the rationale, but we cannot put History section to the top.
 * I would suggest to improve the content of the sections rather than move the sections between them for 21-Hydroxylase and for Histamine N-methyltransferase I like the proposed order of sections in WP:MEDMOS.
 * I do not agree on deleting current information in the "Gene" section for 21-Hydroxylase: the CYP21A2 gene is unique comparing to other genes because it is located in a multimodular cluster, and it should be explained. Even researchers do not understand this topic. I saw many articles where researchers wrote that the CYP21A2 gene is accompanied by CYP21P1 pseudogene, but it is not always the case. In an unimodular structure of RCCX, there is no pseudogene. Quote: In a monomodular structure, all of the genes are functional i.e. protein-coding, but if a module count is two or more, there is only one copy of each functional gene rest being non-coding pseudogenes with the exception of the C4 gene which always has active copies.
 * As for the HNMT, there is the following 3 pieces of information mentioned in the Gene section:
 * Three transcript variants have been identified for this gene in humans, only one has histamine-methylating activity.
 * The cDNA of Hnmt was initially cloned from a rat kidney and has since been cloned from human, mouse, and guinea pig sources.
 * In the human genome, six exons from the 50-kb HNMT contribute to forming a unique mRNA species, approximately 1.6 kb in size. This mRNA is then translated into the cytosolic enzyme histamine N-methyltransferase, comprising 292 amino acids.
 * Do you prefer to move this information to the "Species" section? I think that the "Species" section is more on biodiversity, whereas the "Gene" section is more on exons and intron and other things specific to a gene. I think it will be unfair to delete it.
 * On the functionality/mechanism and equations - I would suggest to keep it as it is for CYP21A2. As for HNMT, yes, there is room for improvement here. We should explain the chemical reaction and give the schematics, and probably also explain more on pathways of histamine metabolism. So, there is lot of work to be done on this section.
 * I will look at Methyltransferase, thank you! Maxim Masiutin (talk) 07:59, 28 November 2023 (UTC)
 * I will also try to delete "These variants arise due to a process called alternative splicing, which allows a single gene to code for multiple proteins by including or excluding particular exons of a gene in the final mRNA produced from that gene"
 * because it makes things complicated to follow, I agree with your observation. Maxim Masiutin (talk) 08:01, 28 November 2023 (UTC)
 * Perhaps a little confusion - I think the CYP genetics - critical, I might have miscommunicated - I totally agree, this is really good data and I had no intention of messing with it - the pseudogene information defines the section - not sure what I stated - but just a misunderstanding.
 * I did not make any changes to it recently. I did mention the activity was highly detailed but it all checks out.
 * Section 3 could be in gene or protein - I tend to think of amino acid counts to be a descriptor of an unfolded protein - but I am old fashioned and I think a molecular biologist would not see it that way.
 * Yes, if it is a required WP format it is fine - a little odd, but I assumed it was defined. BeingObjective (talk) 08:22, 28 November 2023 (UTC)
 * I agree that certain paragraps or sentences can be tossed around sections. If you find a good candidate to move, please feel free to do so! Maxim Masiutin (talk) 09:11, 28 November 2023 (UTC)
 * I moved something to "Species", deleted some common stuff, but left all stuff on substance, so now the "Gene" section is concise. Maxim Masiutin (talk) 08:11, 28 November 2023 (UTC)
 * Yes, this makes sense. BeingObjective (talk) 08:23, 28 November 2023 (UTC)

Function discussion.
@ Maxim Masiutin

I think you stated you might have materials that express this section in a more diagrammatic way - it is text dense, an is arguably a very important section - I looked at the S21H activity area - and a lot of work was done to represent this schematically.

I need to understand the ways other articles work this section - the S21H is especially detailed, I am not totally convinced one has to be that intricate in every article about an enzyme - I guess it depends on the source materials available.

BeingObjective (talk) 14:28, 28 November 2023 (UTC)


 * I think that BogHog may be familiar with the matter. Maxim Masiutin (talk) 15:15, 28 November 2023 (UTC)
 * The WP:MCBMOS gives a few article links as examples:
 * Reelin
 * Estrogen_receptor
 * Alcohol_dehydrogenase
 * These articles are very good on substance, but I don't know whether they fully comply to various Wikipedia rules, I didn't check. Maxim Masiutin (talk) 15:21, 28 November 2023 (UTC)
 * I think this is the very essence of the matter - an article is good - by what real measure?
 * With respect to GA editors - they are following a fairly basic checkbox, and there is still a lot of subjectivity in interpreting GA requirements - sure some aspects are 'clean' assessments - is it appropriately sourced and the like.
 * But, especially on a very technical article, it is a challenge - as you state, the articles that WP:MCBMOS invokes as exhibits, you feel are not compliant - is rule following inhibiting good article production? I have no answer, though being too literal in interpreting what really was only intended as guidance - might be the actual issue.
 * BeingObjective (talk) 17:18, 28 November 2023 (UTC)
 * Yes, that makes sence. I will now try to make drawings for SAM-e and SAH and will try to make drawings of histamine metabolism by HNMT. Maxim Masiutin (talk) 18:13, 28 November 2023 (UTC)

GA Input --The lead is too short and does not adequately summarize the article’s contents
There seems a little concern on what should be in the lede of this article based on the aforementioned GA review.

I think it worth capturing on the article talk page - the original dialog was on my talk page and will get lost in time.

Guidance states  'most' content - I think there is merit in not be too literal, in the following circumstance.


 * 1) When an enzyme is part of a superfamily of enzymes and a robust article already exists talking about the broader family. I think mentioning this in the lede - makes perfect sense - and linking to the parent article.
 * 2) It does not need to be repeated nor deeply discussed in the article body, this seems to add no value - the article is about one member of the enzyme group - mentioning this fact in the lede can hardly violate any guidance - and this is guidance only.
 * 3) The GA review did state the article's lede was light - I think the reviewer was also too literal -
 * 4) One could move it into the body, but it is worth no more than a few sentences no matter where it lives - this applies to any topic when something is a subset of a bigger thing - I think this seems simple common sense - and hardly worth me typing this little diatribe.

Cheers -

BeingObjective (talk) 16:56, 28 November 2023 (UTC)


 * Please see whether this illustration is Histamine_N-methyltransferase? Maxim Masiutin (talk) 20:17, 28 November 2023 (UTC)
 * Well, it is sourced to https://www.rcsb.org/structure/2aot
 * Is there a concern this is not?
 * BeingObjective (talk) 20:38, 28 November 2023 (UTC)
 * I mean the chemical reaction, not the protein structure.
 * [[File:HNMT-methylation-of-histamine.svg]] Maxim Masiutin (talk) 20:42, 28 November 2023 (UTC)
 * Where did you conjure this from? I only note your name and no authoritative academic source.
 * SAM is a cofactor sure - I noted a very similar image in the methyltransferase article - also with no formal academic attribution - did you just take this and put the structures described from the text? Are you sure this is actually compliant with WP policies?
 * Surely you must need to cite this and if understand how you created it - what are you going to cite?
 * Simply not sure about this, if you cannot find a source to cite - it might be prudent not to even include such a diagram - or simplify it so that it is clearly a gross simplification - tricky.
 * BeingObjective (talk) 21:44, 28 November 2023 (UTC)
 * What do you mean by academic attribution? Do you mean that we should back up a claim that histamine goes to N-methylhistamine and SAM-e goes to SAH? I will find source for that. Maxim Masiutin (talk) 22:48, 28 November 2023 (UTC)
 * The reaction is described here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030376/
 * quote: HNMT inactivates histamine by transferring a methyl group from S-adenosyl-L-methionine (AdoMet) to the Nε2 atom of the imidazole ring, yielding methylhistamine and S-adenosyl-L-homocysteine (AdoHcy).
 * We referenced this article when we explained the reaction. Should we also reference it near the drawing, this is what you mean? Maxim Masiutin (talk) 22:57, 28 November 2023 (UTC)
 * There is another source, quote: "Histamine-N-methyltransferase (HNMT) methylates histamine by transferring a methyl group to the imidazole ring, using SAM as the methyl group donor, yielding methylhistamine and SAH. HNMT: SAM + histamine = SAH + N(tau)-methylhistamine""
 * it is a review, therefore, more preferred as a source Maxim Masiutin (talk) 23:09, 28 November 2023 (UTC)
 * If you are happy with this, it is fine. Truly.
 * You actually asked me for a 'reality check' - yes?
 * I do not want to offend you and I am happy to continue a working collaborative relationship - we do not have to agree on every single thing. You have helped me a great deal.
 * I am not sure I can support the way the graphic came to be, perhaps I am totally wrong - recall, I am new and just another general editor - we are not working as collaborators in a formal academic environment.
 * As you stated to me, WP has no 'editor in chief' - if you think this is fine, then has to be.
 * The document is currently FAR better - so let's leave it at that.
 * I would have strongly preferred a schematic with clear provenance - it is not the case - both schematics are 'own work' - I would have liked 'Dr. xyz, UCLA, Biochem, as I communicated to you. I think my concerns were really very clear -
 * Kind Regards Dr. BeingObjective (talk) 00:09, 29 November 2023 (UTC)
 * I don't understand what you mean, frankly. Maxim Masiutin (talk) 01:03, 29 November 2023 (UTC)
 * Can you please help? - can you please help.
 * I saw schemes of histamine methylation by HNMT at these works: ,
 * , and drawn a scheme using Inkscape. To get molecules, I took SMILES from ChEBI and converted them to SVGs and then pasted these SVGs around a sheet, made captions and arrows, and colorful ovals, then put this drawing to the page on Histamine N-methyltransferase, citing those works where I saw similar scheme. Still, Dr. BeingObjective asks about formal academic attribution as required to Wikipedia. There is probably a misunderstanding, can you please help us? Maxim Masiutin (talk) 01:19, 29 November 2023 (UTC)
 * @BeingObjective I guess I wrote about HNMT all I could. Thank you also for your contributions and comments. Should you have suggestions, let me know. Maxim Masiutin (talk) 06:41, 30 November 2023 (UTC)
 * @BeingObjective I guess I wrote about HNMT all I could. Thank you also for your contributions and comments. Should you have suggestions, let me know. Maxim Masiutin (talk) 06:41, 30 November 2023 (UTC)

According to Image use policy: Wikipedia encourages users to upload their own images. The providence of images uploaded to Wikimedia commons is clear when the "created myself" option is used. Using figures downloaded from the web would require a Wikipedia compatible license which is often difficult to find. Also a lot of what is available on the web is low quality. At the same time, it is important to include a source (preferably secondary or tertiary) that confirms what is in the image is accurate. For the reaction catalyzed by histamine N-methyltransferase, one could use KEGG whose layout closely resembles File:HNMT-methylation-of-histamine.svg. Boghog (talk) 04:36, 29 November 2023 (UTC)


 * Thank you! I will put KEGG as a reference. Thank you again for your help! Maxim Masiutin (talk) 04:39, 29 November 2023 (UTC)
 * I will also put these KEGG figures to the image metadata on Wikimedia commons. Maxim Masiutin (talk) 04:40, 29 November 2023 (UTC)
 * @Boghog - I think this part of your response "For the reaction catalyzed by histamine N-methyltransferase, one could use KEGG whose layout closely resembles File:HNMT-methylation-of-histamine.svg." - is at the heart of the concerns I expressed to @Maxim Masiutin.
 * Thanks for the explanation, though still -  'I beleive this looks like what happens', and that is how I read the aforementioned statement you made, seems at odds with WP:RS.
 * This was published without any provenance, despite the robust prior dialog - I was asked in this thread 'does this 'look okay' - and I still would state - why are you even asking me after it was published?
 * Provenance is the correct word, this is really not like stating something and then dropping a robust PMID in to support it.
 * I could not find materials that satisfied my concerns on this 'my own work' issue - and I do not think this requires any further dialog - it is perhaps just a reality of WP.
 * BeingObjective (talk) 14:48, 29 November 2023 (UTC)
 * I think that the term "own work" in this context should be considered from the point of view of the copyright legislation, i.e. the person who drew lines and arranged figures. Underlying information, such as the order of reactions in a chemical process is not copyrightable. Therefore, the term "own work" is applicable here as the term "own work" is understood in the copyright legislation. If you see the image metadata, everything there was about copyright: license, author, whether it is a derived work or an original work, etc. Ideas are not copyrightable, so if I saw similar schemes and draw my own one from scratch it is not considered a derivative work, but my own work. Also, electrocardiogram images are not copyrightable. But if you put an arrow as an explanation, this becomes a work protected by copyright. Maxim Masiutin (talk) 15:00, 29 November 2023 (UTC)
 * I suspect you will not convince me on this matter - KEGG ref. or not - an ECG exhibit is not the same thing and it is nothing about CR - more about Reliable sources
 * Cheers BeingObjective (talk) 15:04, 29 November 2023 (UTC)
 * Apologies - the link should be: Reliable sources.
 * I just see this a weird conflict of the ethos expressed here - even the KEGG ref is a form of weird nebulous editorializing - the credibility of any articles needs to take the editor out of the thing being talked about - is this not the essence of WP?
 * Enough perhaps. BeingObjective (talk) 15:01, 29 November 2023 (UTC)
 * I really don't see what the problem is here. KEGG is a reliable tertiary source.  File:HNMT-methylation-of-histamine.svg is supported that source. Hence my statement is completely consistent with WP:RS.  Full stop.  Ideally the source should have been provided at the same time graphic was inserted into this article, but better late than never. The provenance of the graphic is the editor (Maxim) who created it. KEGG is not editorializing, they are simply summarizing the scientic literature. Boghog (talk) 15:22, 29 November 2023 (UTC)
 * Let's terminate this dialog, enough on the matter.
 * BeingObjective (talk) 15:39, 29 November 2023 (UTC)
 * I already mentioned KEGG and 3 Pubmed sources yesterday in the reference behind the image. Will try to be more specific. Maxim Masiutin (talk) 15:47, 29 November 2023 (UTC)

Pushing electrons
@BeingObjective, @Boghog Can you help me with chemistry? There is a ting that I don't fully understand. In chemistry, a curved (curly) single-headed arrow is used to depict the movement of a single electron from one place to another, either in resonance or in a mechanism. However, in a hystamine methylation, curly arrow on the sources I given (via PMIDs) is from SAMe to SAH. There also a hydrogen atom relesed, but it is not shown on reaction. However, I couldn't find any specific information about the use of a curved arrow to distinguish a cosubstrate transformation from the main substrate transformation. Does the electron move from SAMe to SAH in this reaction? Maxim Masiutin (talk) 15:15, 29 November 2023 (UTC)


 * It is important not to confuse a biochemical reaction schematic (where the arrows can either be straight or curved), and an "electron pushing" reaction mechanism, where the movement of a pair of electrons is represented by a curved double barbed arrow and the movement of a single electron is represented a single barbed arrow. File:HNMT-methylation-of-histamine.svg is a biochemical reaction schematic and the curved arrow in it does not imply the movement of a single electron. Boghog (talk) 15:35, 29 November 2023 (UTC)
 * Is there a nomenclature described on biochemistry? It is not a coincidence that 3 sources used curly arrow for cosubstrate transofrmation? Where can I read about it? Maxim Masiutin (talk) 15:46, 29 November 2023 (UTC)
 * Oops, hydrogen is released in case of diamine oxidase reaction (DAO aka AOC1) on histamine, not in case of HNMT. Sorry for confustion. Maxim Masiutin (talk) 15:49, 29 November 2023 (UTC)
 * From my quick googling, it appears that most methyltransferases (including histamine N-methyltransferase) catalyze the classical (non-radical) SN2 mechanism where histidine acts as a nucleophile and SAM acts as a electrophile. There are a few methyltransferases that catalyze a radical mechanism that requires a [4Fe-4S] cofactor. Boghog (talk) 15:58, 29 November 2023 (UTC)
 * There is an interesting notion at https://bio.libretexts.org/Bookshelves/Biochemistry/Fundamentals_of_Biochemistry_%28Jakubowski_and_Flatt%29/01%3A_Unit_I-_Structure_and_Catalysis/06%3A_Enzyme_Activity/6.05%3A_Enzymatic_Reaction_Mechanisms
 * See Figure 6.5.2 : Class I methyltransferase mechanism alternative arrow pushing
 * There is a description of the use of arrow in a reaction from SAMe to SAH, still, a bit complicated convention Maxim Masiutin (talk) 16:01, 29 November 2023 (UTC)
 * It seems that I have to make arrow from methyl group probably. Let me try. Maxim Masiutin (talk) 16:02, 29 November 2023 (UTC)
 * Some more information is here which shed light on this arrow conventions: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491745/ Maxim Masiutin (talk) 16:07, 29 November 2023 (UTC)
 * Another way of thinking about it, in a reaction schematic, the arrows point at molecules that are consumed or created. In a reaction mechanism, the arrows point a individual atoms and the arrows themselves represent a flow of electrons, where a single barbed arrow represents the movement of a single electron and a double barded arrow represents the movement of a pair of electrons. Boghog (talk) 16:32, 29 November 2023 (UTC)
 * OK, that makes sense. I just made the two arrows connect each other to show that it is a single reaction. Maxim Masiutin (talk) 17:13, 29 November 2023 (UTC)
 * Can you please now review the caption behind the image in the "Function" section of the article (Histamine_N-methyltransferase). I hope that it is now more than reasonable, both on citing sources and on explaining what the arrows mean. Maxim Masiutin (talk) 17:19, 29 November 2023 (UTC)

Britannica as a source
@Sammi Brie - I have a follow-up question. You wrote that Britannica is not a good source. Can you please provide the reasoning for that? Thank you! Maxim Masiutin (talk) 16:10, 28 March 2024 (UTC)

Did you know nomination
This subsection is transcluded from Template:Did you know nominations/Histamine N-methyltransferase.
 * The following is an archived discussion concerning one or more templates or modules. Please do not modify it. Subsequent comments should be made on the appropriate discussion page (such as the template's talk page or in a deletion review).

The result of the discussion was delete.
 * The above is preserved as an archive of the discussion. Please do not modify it. Subsequent comments should be made on the appropriate discussion page (such as the template or module's talk page or in a deletion review). No further edits should be made to this section.

Explanation of uncommon terms
Hello, User:AstonishingTunesAdmirer, User:AryKun, User:David Eppstein, I followed your suggestions at https://en.wikipedia.org/w/index.php?title=Wikipedia_talk:Good_article_nominations&oldid=1217067219#Hard-to-understand_terms_in_the_lead and replaced uncommon terms in the lead and in the body that you pointed out. Can you please provide your feedback on the following changes:


 * 1) Removed the word "cytoplasmic" from the lead and added description to the "Protein" section on what is the cytoplasmic protein and what is a cytoplasm. The word "cytoplasmic" did not add value to the lead section. It was not essential. The lead without this word did not lose any value.
 * 2) Replaced the term "biogenic amine" in the lead to "biomolecule", because it was not essential in the lead to qualify "histamine" as a "biogenic amine". Even without such qualification the lead did not lose its value. Instead, I made a description on what is a "biogenic amine" in a later section, and defined a biogenic amines as "substances, produced by a life form (like a bacteria or an animal) that has an amine group (−NH2)."
 * 3) Explained the term "knockout mice" in the lead, the following way "genetically modified mice lacking the Hnmt gene".
 * 4) Explained the term "histaminergic neurotransmission" in the lead and in the body.
 * 5) Also explained a few terms in the sections.

See https://en.wikipedia.org/w/index.php?title=Histamine_N-methyltransferase&diff=1217089317&oldid=1215724083

Maxim Masiutin (talk) 18:59, 3 April 2024 (UTC)
 * In my opinion, it is easier to understand now for an average reader. Nice job! Also I believe you meant to ping .  AstonishingTunesAdmirer 連絡 19:30, 3 April 2024 (UTC)

Replace first#/last# to vauthors
Hello, @Boghog! Can you please help with editing this article by replacing all instances first#/last# to vauthors? Thank you in advance! Maxim Masiutin (talk) 08:06, 20 April 2024 (UTC)