Talk:Enzyme inhibitor

Merge

Hello!

I seem to have created two related but not identical articles. Enzyme inhibitor, started earlier by User:Edgar181 explains inhibition at the protein level, while enzyme induction also explains enzyme inhibition, but at the genetic level, and relates more to pharmacology. This was really necessary because a lot of pharmacology articles had redlinks to enzyme induction and enzyme inhibition, the latter referring to the article I started.

In the introduction of the article I started, I mention the problem and have a redirect to the other article. I created a redirect to enzyme induction from enzyme inhibition, which he changed (in good faith) to enzyme inhibitor.

What is the best way to solve this problem? I can think of various ways but I'm not sure what is the best option, so I wanted to ask here.

1. Merger of the two articles. This is probably the option I prefer.
2. Creation of a disambiguation page.
3. Put a message above each article referring to the other article.
4. Put an explanation of the two levels in the inhibitor article, with a referral to enzyme induction.
5. The same could be done in a "see also" section, but this is not the option I prefer.
6. Another option?

I am aware of the current bad title for enzyme induction, which should be enzyme induction and inhibition, I think. But then the explanation about enzyme inhibitors would kinda not fit under this title. As you can see I'm struggling, please help out! :-)

I'm on wikibreak myself starting from tomorrow, so I'll catch up at the end of July.

kind regards, --Steven Fruitsmaak 18:39, 3 July 2006 (UTC)

Enzyme induction is an example of the control of gene expression. I think the Enzyme Induction page should therefore be merged with gene expression which gives more examples of this process and mentions how it happens.--TimVickers 19:23, 3 July 2006 (UTC)

I don't think this is a realistic option. If it would resort under such a header, I would suggest it to be split into seperate articles. It is indeed an example, but also a topic important enough on itself to deserve an independent article outside gene expression. But I conclude from your remark that you think it has little to do with inhibition at the enzyme level, and that you oppose to the merger? --Steven Fruitsmaak 19:57, 3 July 2006 (UTC)

Well, enzyme induction is just one particular type of the thousands of changes in gene expression which organisms can make in response to their environment. It seems quite separate from interactions of chemicals with these proteins after they have been synthesised. So yes, I do oppose the merger. However, I think your suggestion of a disambiguation page could work very well, since these terms sound quite similar and could indeed be confused.--TimVickers 20:27, 3 July 2006 (UTC)

My preference would be something similar to option 4 above. Enzyme inhibitor and enzyme induction are clearly related articles, but I think the topics are distinct enough to warrant separate articles. I don't have a problem with both the articles reproducing some information from the other. I think each article with continue to grow and become more thorough and they will gradually diverge in content. If they are merged now, it would make a good article, but in the near future there will be probably end up being a split anyway. So I would suggest just having the two articles refer to each other. --Ed (Edgar181) 13:11, 8 July 2006 (UTC)

Option 4 it is!--Steven Fruitsmaak | Talk 10:14, 31 July 2006 (UTC)

I am going to pu this up for Peer review as soon as the Enzyme kinetics article is off the list. TimVickers 22:20, 29 August 2006 (UTC)

Merging or disambiguation is fine when the ultimate article contains the information the user seeks. In this article, however, there is only scant mention of induction at all! In fact, the only mention is:

Some, such as anti-epileptic drugs, alter enzyme activity by causing more or less of the enzyme to be produced. These effects are called enzyme induction and inhibition and are alterations in gene expression, which is unrelated to the type of enzyme inhibition discussed here.

How can this article be considered the authoritative source for information about enzymatic induction when it never discusses it? Gjbloom (talk) 01:16, 17 August 2008 (UTC)

Non-competitive inhibition

As the article currently reads:

Non-competitive inhibition is a sub-set of mixed inhibition.

Is this really true? I would not consider non-competitive inhibition as a sub class of mixed inhibition. We need to be very careful here since non-competitive inhibition is very common in the text books. One might ask why, since it is very rare. In fact, I'm not sure I can even give one example. My feeling is that historically this is a convenient defintion to complement competitive inhibition. While competitive inhibition only changes the Km non-competitive only changes the Vmax. This is all well and good from a theoretical perspective, but since such inhibitors do not really exist it gets confusing. Personnally I think adding them to the mixed category is a recent academic cop out that is a misschacterisation of non competitive kinetics. What do others feel about this? This is clearly a contentious issue and I have heard many differing opinion from biochemists on this issue. In reality it is quite amazing that this concept is still taught. David D. (Talk) 16:39, 18 September 2006 (UTC)

I think including it is a useful pedagogical trick, but it doesn't have many practical applications. TimVickers 20:09, 20 September 2006 (UTC)

I certainly agree its absense would be obvious. And it is clearly present in the text books for that reason. David D. (Talk) 20:12, 20 September 2006 (UTC)

Unfortunately the entire article is really a mess. The treatment of enzyme kinetics is outdated at best and in places incorrect. I am also not sure why an article for "enzyme inhibitor" largely repeats what is already covered under "enzyme kinetics". But in this one aspect this article is actually correct: Mixed inhibition is the most general type of inhibition; competitive, non-competitive and uncompetitive inhibitions are just special cases obtained by setting certain rate constants to zero. See Cleland' series of papers (BBA 67 (1963) 104–137, 173–187, 188–196) for the first modern treatment of enzyme inhibition. This material is also covered in several books (e.g., Bisswanger 2002, Cook & Cleland 2007, Buxbaum 2007) and by a nomenclature draft standard of IUBMB/IUPAC (http://www.chem.qmul.ac.uk/iubmb/kinetics/). The German Wikipedia on enzyme kinetics is also nice (http://de.wikipedia.org/wiki/Enzymkinetik). —Preceding unsigned comment added by 207.42.135.25 (talk) 19:38, 23 November 2010 (UTC)

Not inhibitors

I wonder if the intro should focus so much on what is 'not an enzyme inhibitor'. It seems to take up a lot of space. I am considering moving it to the drug section in the article and reducing it to a short disclaimer in the introduction. David D. (Talk) 16:45, 18 September 2006 (UTC)

Sounds a good idea, particularly the stuff on induction/repression. I've moved this to Chemotherapy. TimVickers 20:09, 20 September 2006 (UTC)

I'd forgotton i wrot ethe above since most of the discussion was on the FA nomination page. What you just did is exactly what was needed. David D. (Talk) 20:20, 20 September 2006 (UTC)

Section on ion-channels

Moved until I can find where to put it.

Other familiar neurotoxins include tubocurarine, a competitive neuromuscular blocker of nicotinic acetylcholine receptors, that is the source of arrow poison and was used for anaesthesia. Coniine, an alkaloid found in poison hemlock, has a neurotoxic effect similar to tubocurarine and is infamous as the poison used to kill Socrates.

Toxins that block ion channels can also interfere with neural function. Tetrodotoxin, from pufferfish (Fugu), is a particularly potent inhibitor of the voltage-gated sodium channels in nerve membranes. This halts action potentials since it mimics the hydrated sodium ion and blocks the pores. According to William Light: Weight-for-weight, tetrodotoxin is ten times as deadly as the venom of the many-banded krait of S.E. Asia. Tetrodotoxin is 10 to 100 times as lethal as black widow spider venom, and more than 10,000 times deadlier than cyanide. It is interesting to note that although this toxin is associated with Fugu, it appears to be synthesised by bacteria. Fugu are immune to the toxin due to a single point mutation in their sodium channel that prevents the specific binding of the toxin. Another ion channel inhibitor is digoxin, from the foxglove plant (Digitalis), that competes with potassium ions for the binding site on the Na⁺/K⁺ ATPase pump. Digoxin is a cardiac glycoside with many symptoms, including heart arhythmia, nevertheless, it has been widely used in the treatment of various heart conditions such as atrial fibrillation.

The natural poisons section does look more balanced with its absence. David D. (Talk) 20:16, 20 September 2006 (UTC)

References

oops

I meant to revert TO MisfitToys, not past. Thanks for putting back. –Outriggr § 00:54, 15 December 2006 (UTC)

Activity?

How about we change the word from activity in the first paragraph to "catalysis"? Its far more scientific and in the wikipedia definition, catalysis includes biological catalysts, which are enzymes. —The preceding unsigned comment was added by 68.6.230.65 (talk) 03:22, 15 December 2006 (UTC).

There may be confusion if you say a compound blocks "catalysis" as this could be read either to be blocking turnover, or just the catalytic step. I'd prefer activity, which can't be interpreted in this specific way. TimVickers 04:24, 15 December 2006 (UTC)

Vandalism

Does anyone else see an absolutely disgusting picture of a very weird looking penis that blocks the top of the article? I tried to edit it out but I can't find the source of it. --Surelyican 03:51, 15 December 2006 (UTC)

It's in the templates and images - been going on for several days. Admins are working on it. Sandy (Talk) 03:53, 15 December 2006 (UTC)

Eadie-Hofstee Plots

Since we have Lineweaver-Burk plots of the different inhibitions up, should we also include their Eadie-Hofstee plots as well?

The L-B plots are only there for historical purposes, since nobody uses them for data interpretation and they are only used occasionally for data presentation. I have never seen a E-H plot in a modern journal article, so I really don't think people will come across them. TimVickers 16:21, 15 December 2006 (UTC)

How do you control inhibitors on enzymes

Could someone please answer the above question. Cheers Ahadland 19:00, 3 March 2007 (UTC)

I'm not sure what you mean, do you want to know how a particular binding site is selected and why inhibitors don't bind randomly onto the surface of enzymes? TimVickers 02:07, 4 March 2007 (UTC)

The references

In the references, the article names are in italics and the journals names are not. It should be the other way around, according to convention. Is there a special reason for this here? Pixie 18:02, 24 July 2007 (UTC)

No, you're quite welcome to format these with the cite template. Not a task I'm keen on taking up myself! Tim Vickers 18:06, 24 July 2007 (UTC)

Feedback inhibition

I've redirected feedback inhibition here, as it is only used for enzymes as far as I know. But there isn't actually that much on this here - perhaps there should be a section devoted to this type of inhibition? Aspects like the way the final product inhibits the initial enzyme, preventing the creation toxic intermediates could be discussed. Richard001 07:24, 2 August 2007 (UTC)

Feedback inhibition is a function of some reversible inhibitors. Discussion of this function might be expanded a little in the "Metabolic control" section, but it is not mechanistically different from other types of reversible inhibition. Tim Vickers 16:25, 2 August 2007 (UTC)

Problem with your inhibition

Your figure of non compeditive inhibition is wrong you may want to correct this. The slope i.e (Vmax/Km) does not change in this plot —Preceding unsigned comment added by 134.53.132.215 (talk) 15:43, 13 October 2007 (UTC)

You mean this one: Image:Inhibition_diagrams.png? Are you sure you're not mixing up uncompetitive inhibition with non competitive? David D. (Talk) 07:57, 16 October 2007 (UTC)

I think there's confusion between non-competitive, uncompetitive, and mixed. Some literature uses non-competitive and mixed interchangeably. Regardless, uncompetitive inhibition should be including, especially it's Lineweaver-Burk plot. --Dooser (talk) 02:24, 5 March 2008 (UTC)

Uncompetitive is when the inhibitor will only bind to the ES complex, the L-B plot is shown in figures 2 and 3 of this paper - parallel lines that do not intersect. This is a very rare mode of inhibition, so isn't included in the diagrams on this page, but we should probably have a diagram of this in the uncompetitive inhibition article. Tim Vickers (talk) 05:34, 5 March 2008 (UTC)

I've added one to that article. Tim Vickers (talk) 19:44, 5 March 2008 (UTC)

Dab entry at Ki

In place of this entry at the Dab'n pg KI

*[[Enzyme inhibitor|K_i]], enzyme inhibition

which is clearly contrary to MoSDab bcz of the piping, i put instead

• K_i, symbol for effectiveness of enzyme inhibitor

with "symbol for" as a shot in the dark. It's still not acceptable, bcz K_i (AFAI can see) the article isn't on K_i, K_i doesn't even get mentioned above the third heading (4 screens down from the top of the page), AFAI can see K_i isn't even described, but merely used. Should the entry be converted to some kind of lk to a new section of Dissociation constant, where it could be explained why enzyme inhibition is a case of dissociation, or dissociation a process competitive to dissociation?
--Jerzy•t 01:37 & 01:41, 13 July 2008 (UTC)

HDAC inhibitors

Should this page should mention HDAC inhibitors ? and if so, where ? Rod57 (talk) 18:19, 30 November 2008 (UTC)

I guess it would be under Uses but probably HDAC inhibitors are not important enough to be mentioned. Any idea why Acetylcholinesterase is the only enzyme that gets its own section under Uses ? Rod57 (talk) 04:07, 20 January 2010 (UTC)

My guess would be that it was added by somebody who worked on AChE inhibitors and thought they were very important. This is a bit imbalanced, so I've renamed this "pesticides and herbicides" and will add a broader range of examples. 19:22, 20 January 2010 (UTC)

Merge w/ receptor antagonist?

Should receptor antagonist be merged with this enzyme inhibitor? Temporal User (Talk) 00:21, 25 January 2009 (UTC)

Certainly not! I'm taking down the tags. Narayanese (talk) 00:26, 25 January 2009 (UTC)

Oh, I forgot to give a reason. The articles are on subjects that don't overlap much. Length is also an issue. Narayanese (talk) 11:36, 25 January 2009 (UTC)

No, receptors are not usually enzymes. Tim Vickers (talk) 01:29, 25 January 2009 (UTC)

Feedback Control redirect

Why does Feedback control redirect to this article? Feedback control is the name of a large field of technology related to electronics and robotics and essentially unrelated to enzyme inhibitors. I would suggest a redirect to Control Theory instead. ~~me —Preceding unsigned comment added by 204.4.70.37 (talk) 17:05, 16 September 2009 (UTC)

I've redirected it to Feedback. Tim Vickers (talk) 17:56, 16 September 2009 (UTC)

Useful additions

There is nowhere here that explains what km and vmax are, and the page on Michaelis–Menten kinetics is too detailed to make it easy to understand the significance of these terms. Their meanings can be deduced from the examples, but that's it. I suggest links to relevant pages. Also, a Lineweaver-Burk plot for uncompetitive inhibition seems like an obvious addition. An image of one already exists on that page. 143.239.192.26 (talk) 16:01, 2 May 2010 (UTC)

Clarification request

From the article: "Irreversible inhibitors usually react with the enzyme and change it chemically. These inhibitors modify key amino acid residues needed for enzymatic activity. In contrast, reversible inhibitors bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind the enzyme, the enzyme-substrate complex, or both."

I assume this means irreversible inhibitors bond covalently. I think it's safe to assume, but I'd like to be absolutely certain.

Blafreniere (talk) 01:42, 14 October 2010 (UTC)

Actually, "irreversible inhibitor" is an oxymoron, inhibition is by definition always reversible. Irreversible processes are called "inactivation". Inactivators usually form covalent bonds to the enzyme, but for example the interaction of metal centers with cystein or histidine side chains can be strong enough to be virtually irreversible. I have written my PhD thesis about such a case. —Preceding unsigned comment added by 207.42.135.25 (talk) 19:45, 23 November 2010 (UTC)

Help with related articles on types of reversible inhibition

This article, thankfully, seems to get the definitions of competitive, non-competitive, uncompetitive, and mixed inhibition exactly right. However, the articles on those specific kinds of inhibition are a mess, largely because there is a lot of misinformation all over the internet about the exact definitions. For example, the article on non-competitive inhibition currently says that a non-competitive inhibitor is any inhibitor that does not bind to the enzyme's active site. That will be fixed in a few minutes, but I could really use some help bringing the other articles in line with the definitions presented here and backing those definitions with solid sources. I suspect it could be a contentious issue as there are tons of sources out there that back the incorrect definitions. mcs (talk) 03:52, 2 April 2012 (UTC)

"Term used to describe"

I've been going through Wikipedia articles and removing the phrase "term used to describe" where I can since it's usually unhelpful fluff; sometimes, I simply change it to "term used to refer to" since terms don't normally describe. This effort has brought me to in this article (as well as enzyme kinetics) with the following sentence:

While this terminology results in a simplified way of dealing with kinetic effects relating to the maximum velocity of the Michaelis–Menten equation, it highlights potential problems with the term used to describe effects relating to the K_m.

It seems like this could be changed to "term referring to" but I honestly don't know what that sentence is talking about. Could someone who does know tell me if that change would be wrong and, if so, what "term" means in that sentence? — Ƶ§œš¹ _{[ãːɱ ˈfɹ̠ˤʷɪ̃ə̃nlɪ]} 22:53, 5 December 2012 (UTC)

WP:URFA/2020

This featured article, last reviewed in 2006, has turned into quite a wreck since Tim Vickers stopped editing; unless someone is able to bring it to WP:WIAFA standard (and fix the image layout mess, too), the article should be submitted to WP:Featured article review. SandyGeorgia (Talk) 20:54, 13 December 2020 (UTC)

Can you be a little more specific? This is one area that I am somewhat familar with. I think the chemotherapy section needs to be complemented with a targeted therapy (e.g., imatinib, etc.) section. Also the sources throughout need to be updated and the images with black background should be replaced with transparent backgrounds. What other problems are there? Boghog (talk) 00:43, 26 March 2022 (UTC)

The following is an archived discussion of a featured article review. Please do not modify it. Further comments should be made on the article's talk page or at Wikipedia talk:Featured article review. No further edits should be made to this page.

The article was kept by Nikkimaria via FACBot (talk) 2:32, 6 August 2022 (UTC) [1].

---

Enzyme inhibitor

Notified: TimVickers, Molecular Biology, Pharmacology, talk page notification 2020-12-13

This was noticed near the end of 2020, there is a bunch of problems with the articles. Unsourced sentences, the images are laid out messily, the writing needs a overhaul. There are a lot of issues with this article that I don't think will be fixed. GamerPro64 23:02, 25 March 2022 (UTC)

I have reordered a few of the sections, corrected a few inaccuracies, improved the image layout, and have added a few citations. I will add more as I find time. Any additional problems? Boghog (talk) 14:23, 26 March 2022 (UTC)

Definitely looks improved from the previous version. Gonna need another take from someone more seasoned with medical articles at least. GamerPro64 04:44, 29 March 2022 (UTC)

@Boghog: I am not a medical expert (maybe SandyGeorgia can suggest a couple of editors to take a look at this?) but I'll give some general thoughts below as a non-expert reviewer. I noticed that there's lots of paragraphs that either do not have citations or do not have one at the end. When I write historical bios, I typically require a citation at the end of the every paragraph, minimum, to verify the preceding information. I'm not sure how it is with MED articles, as there are formulas involved, so instead I will post some of these paragraphs without citations below:

• There's a couple of paragraphs that do not have citations that concern me. One place is the "Types" section (under "Reversible inhibitors"): uncompetitive inhibition has a citation at the end of its paragraph but the other do not. What is verifying the information in the other three paragraphs, and should there be a citation at the end of them?
• Under "Quantitative description" there are paragraphs between formulas that are not cited. I am confused about which sources are verifying this information. Is there a way that citations can be added to these paragraphs?
• The first paragraph in "Measuring" does not have citations. Is citation 33 verifying this information?
• The first paragraph in "Applications" does not have citations. What is verifying this information?
• The second paragraph in "Antibiotics" does not have citations. What is verifying this information?
• The first paragraph in "Pesticides" does not have citations. What is verifying this information?

I hope this gives a good start in things to consider. Please ping me if you have any questions. Z1720 (talk) 03:30, 3 April 2022 (UTC)

Thanks Z1720 for your comments. I am gradually adding more citations to the sections that you mention. Under the Quantitative description section, the second half of the section was added after the the article was promoted to FA in this edit, is fairly technical, and the only support I could find was in a predatory source. Prehaps it would be best to delete this material altogether. Boghog (talk) 10:24, 3 April 2022 (UTC)

I do not have the subject-area expertise to comment on what should and should not be in the article, so I will defer to other's judgement. Z1720 (talk) 15:30, 3 April 2022 (UTC)

There is too much text uncited that should be cited, inappropriate use of bolding, and while I am not easily frightened by biomedical topics, I can get no sense from the lead of ... anything. The lead needs to be brought down a level, into plainer English, less jargon. SandyGeorgia (Talk) 00:28, 4 April 2022 (UTC)

Thanks SandyGeorgia for your comments. Most material is now supported by citations, inappropriate bolding removed, and the lead has undergone signficant copyedits, so hopefully it is now more accesssible. Boghog (talk) 12:13, 9 April 2022 (UTC)

I haven't read through yet.

• Is interfers British spelling?
• "For example, in the Lineweaver–Burk plots at the right, ... " nothing at the right ... so a complete read-through is needed.

SandyGeorgia (Talk) 13:43, 9 April 2022 (UTC)

I updated the lead to make it more accessible for laypeople and corrected some minor misspellings and whatnot. Surprisingly, „interfers“ is not (yet) accepted British spelling. But I daresay it will be someday, as a posher variant of gofers — looks better on a résumé, no? ;)

I also clarified the text regarding the Lineweaver-Burk plots, to make it easier to recognize which diagrams are meant and how they illustrate the type of inhibition (competitive vs. non-competitive).

I've also done a quick scan through the article to find mistakes, but not yet a thorough read-through. Willow (talk) 10:38, 16 April 2022 (UTC)

I am going to be traveling for my son's wedding, and won't be able to follow progress on this nom for several weeks, but on a quick final glance I see:

• Paragraphing in the lead makes no sense and it is still not lay-reader friendly.
• WP:CITATION OVERKILL ... maximum reaction rate catalyzed by the enzyme) and Km (the concentration of substrate resulting in half maximal enzyme activity) as the concentration of the enzyme's substrate is varried.[2][4][5][6][7]: 132–167 
• Still some text that is uncited that needs citation.
• Still some MOS:BOLD wonkiness.
• A complete read-through is needed.

GamerPro64 I won't be available to help bring this one over the line. Perhaps you can enlist Graham Beards? SandyGeorgia (Talk) 13:52, 21 April 2022 (UTC)

Thanks SandyGeorgia for your constructive comments. Concerning the lead, for context, it should brefily put in context what an enzyme is and why it is important, but perhaps it could be trimmed back a bit to focus more closely on inhibitors, and that might make it a bit easier to digest. Concerning the single bolded term that is not in the lead sentence, covalent reversible inhibitors is a redirect, and hence is an allowed exception to MOS:BOLD. I will work on adding more citations to other parts of the article and remove citation overkill. Congrats to your son and enjoy your trip! Boghog (talk) 16:15, 21 April 2022 (UTC)

Thanks! I can follow from iPad, but can't do much to help. SandyGeorgia (Talk) 17:28, 21 April 2022 (UTC)

• Could we get an update on status here? Nikkimaria (talk) 04:20, 7 May 2022 (UTC)

  I think all the concerns raised above have now largely been addressed. If there are any remaining issues, please let me know and I will try to fix them. Just one note in passing. Above it was suggested that we need a medical review. However, with the exception of the Enzyme_inhibitor#Drugs section, this article is more within the scope of WP:MCB than WP:MED. Boghog (talk) 06:54, 7 May 2022 (UTC)

  This section (for example, natural poisons and drugs) contains biomedical/health statements that I don't feel qualified to assess; the article needs a medical reviewer. SandyGeorgia (Talk) 21:10, 1 June 2022 (UTC)

  Reliable secondary sources should be sufficient to support statements about poisons. We are not going to run randomized double blinded clinical studies to confirm that exposure to nerve gas causes deaths in humans. That would obviously be unethical. Animals studies + ancidotal human evidence is more than sufficient. Statements such as 1/3 of currently approved drugs are enzyme inhibitors are uncontroversial and are backed up by reliable secondary sources already included in the article. Boghog (talk) 19:09, 5 June 2022 (UTC)

• Acronyms are used before they are defined (eg, ATH, NADH); check throughout needed. SandyGeorgia (Talk) 20:53, 1 June 2022 (UTC)

  Hopefully I caught all the remainder in this series of edits. Boghog (talk) 10:19, 5 June 2022 (UTC)

• User:Evad37/duplinks-alt reveals a number of duplicate links, but they are probably justifiable by the complexity of the topic; I have rejigged to avoid some Easter egg links, and that should be checked throughout. SandyGeorgia (Talk) 20:54, 1 June 2022 (UTC)
• The lead image and caption are not explaining to the layreader what an enzyme inhibitor is, rather providing too much detail that isn't helpful to the lay reader, who will access the lead. SandyGeorgia (Talk) 20:56, 1 June 2022 (UTC)

  • @Evolution and evolvability:. Your figure is beautiful and a big improvement over the figure that it replaced, but is not as dead simple as it should for the lead of a featured article. I can simplify the caption, but I am not nearly the artist that you are. Something similar to this might get the point across more clearly. Can you make something similar? In addition, something like this figure would be great further down the article. Cheers. Boghog (talk) 18:44, 3 June 2022 (UTC)

    I agree - It probably makes sens to have a highly sinplified variant for the lead image. I'll get on it this week. T.Shafee(Evo&Evo)^talk 10:04, 5 June 2022 (UTC)

  Thanks! I have put in place holder "pac-man" figures, but please feel free to replace. Cheers. Boghog (talk) 16:58, 5 June 2022 (UTC)

  I've added some updated figures throughout, aiming to use similar colour schemes to those used in enzyme. I've also edited the kinetic mechanisms to use the K_i' making system (rather than the old K_ii nomenclature) as I think it's more common these days. A number of publications use the αK_i nomenclature, but it's used inconsistently and more complex inhibitor suituations use a different nomenclature again (example) I've also tried to make the italicisation consistent, but please do check if I've missed any! T.Shafee(Evo&Evo)^talk 07:56, 13 June 2022 (UTC)

  The new graphics are perfect! Both dead simple and visually pleasing. Also thanks for your other edits. Cheers. Boghog (talk) 10:36, 13 June 2022 (UTC)

  No worries! I might also try to make something for metabolic regulation within pathways (including end-product regulation) as I think it's easiest when visualised. T.Shafee(Evo&Evo)^talk 12:46, 13 June 2022 (UTC)

  • I have inserted a simplifed figure (File:Enzyme inhibitor.svg) and caption, that while not as pretty as the original, hopefully it is dead simple and appropiate for a lay reader. Boghog (talk) 19:45, 4 June 2022 (UTC)
  • I have also added a second figure File:Enzyme inhibitor types.svg in this edit. Boghog (talk) 09:33, 5 June 2022 (UTC)

• I have removed external jumps from image captions and completed incomplete image captions: this citation needs to be completed. Unsure if that should be a cite web or a cite journal. SandyGeorgia (Talk) 21:06, 1 June 2022 (UTC)

  It is both a journal citation and a Protein Data Bank entry. Added both in this edit. Boghog (talk) 19:25, 3 June 2022 (UTC)

• A short description of why each item is included in See also would be helpful. SandyGeorgia (Talk) 21:11, 1 June 2022 (UTC)

  Added in this edit. Boghog (talk) 19:25, 3 June 2022 (UTC)

• Unique sub-headings: the heading "Examples" is used twice. SandyGeorgia (Talk) 19:31, 3 June 2022 (UTC)

  Not sure how to address this. The "Types" and "Examples" subheadings are used twice, but they are under different headings, "Reversible" and "Irreversible", so it is implied that the headings mean "Reversible types", "Irreversible examples", etc. We could spell out the implied meaning, but that would violate WP:HEAD (don't repeat heading titles in every subheading). Alternatively, a synomyn could be used, but I cannot think of any good synomyms to use in this context. Boghog (talk) 09:23, 5 June 2022 (UTC)

  I think it's reasonable to repeat subheadings under different headings in this context, and the shorter Types subheadings are definitely better than Types of reversible inhibitors etc. T.Shafee(Evo&Evo)^talk 12:18, 13 June 2022 (UTC)

  It is a bit problematic though, as it messes with section linking processes. Enzyme inhibitor#Types will always go to the first use of the section heading. Hog Farm _Talk 13:38, 20 June 2022 (UTC)

  I have addressed that issue; there are still remaining issues. MOS:SEEIMAGE. Throughout, the text refers to image placement with words such as "on the right", etc. Images display in different places on different browers; this needs to be redone. @Buidhe, Hog Farm, and Z1720: do you find the lead accessible to a layperson? SandyGeorgia (Talk) 15:10, 20 June 2022 (UTC)

  I'll give it a read-through over my lunch break. Hog Farm _Talk 15:11, 20 June 2022 (UTC)

  I found it comprehensible. Hog Farm _Talk 17:37, 20 June 2022 (UTC)

• While complying with MOS:COLOR can often be difficult, and not a reason alone for opposing an image, it is awkward to have a lead image that breaches MOS:COLOR and that contains excess information. A simpler lead image is still needed. SandyGeorgia (Talk) 15:16, 20 June 2022 (UTC)

  The bottom row of the lead graphic (File:Enzyme inhibitors.svg) depicts allosteric inhibition and is not directly discussed in the lead. I have therefore replaced it with a new version (File:Enzyme inhibitors 2.svg) which removes the bottom row. I think the remaining information is very relevant to the lead and does not contain any excess information. The top row depicts what an enyzme does (first paragraph of lead), and the bottom row depicts how an inhibitor works (second paragraph of lead). The current colors do not pass the contrast standards for the color impaired. However the graphic does contain symbols for enzyme (E), substrate (S), product (P), and inhibitor (I). I have added these symbols to the caption. Boghog (talk) 10:13, 24 June 2022 (UTC)

• A jargon check/wikilinking check is needed throughout; eg, isomerization, Acetylcholinesterase inhibitor doesn't seem to be linked. Pls check throughout. SandyGeorgia (Talk) 15:19, 20 June 2022 (UTC)

  I have added a number of wiki links for technical terms and provided explained what a dissociation constant is in this edit. Boghog (talk) 11:11, 25 June 2022 (UTC)

• Review throughout for MOS:CURRENT issues; time context is needed for statements like "More recently, an alternative approach has been applied: rational drug design uses the three-dimensional protein structure of an enzyme's active site to predict which molecules" ... something like ... since the 1970s, in the 21st century, etc. Similary, missing as of dates, sample: "currently approved drugs are enzyme inhibitor". Similarly, but also indicating the article is still dated: "repeated until a sufficiently potent inhibitor is produced.[95] Computer-based methods of predicting the affinity of an inhibitor for an enzyme are also being developed, such as molecular docking" is cited to 2003: "also being developed" still ??? Updates needed. Another example of a MOS:CURRENT, missing as of date, is: "An estimated 29% of currently approved drugs are enzyme inhibitors[74] of which approximately 1/3 are kinase inhibitors."

• Concerning MOS:CURRENT, in this edit, I specified when. Concerning molecular docking which was mentioned in the Discovery and design of inhibitors section, the entire section was out-of-date and read like an advertisement for virtual screening. While virtual screening is useful, it is only one many strategies that are used in modern drug disocovery. Therefore I have completely rewritten this section based on more recent secondary sources. Hopefully the section is now more balanced. It needs some additional copy edits and I am working on this. Boghog (talk) 11:20, 25 June 2022 (UTC)

This issues indicates that a top-to-bottom check for WP:WIAFA compliance and comprehensive rewrite has not yet been done. Shall we MOVE to FARC or is someone able to do a comprehensive check and update? SandyGeorgia (Talk) 15:28, 20 June 2022 (UTC)

Thanks again for your constructive criticisms. All issues that have been identified above have been fixed. The introduction section was not as accessibe as it should have been, but it has been extenstively rewritten and now it should be understandable to a wide audience. The Drugs section was also rewritten to bring it up-to-date and to broaden its scope. The Discovery and design of inhibitors section had some neutrality issues and also was not up-to-date. This section has been completly rewritten to adress these concerns. I have gone over the rest of the sections and in my opinion, they look like they are in good shape. Basic enzymology concepts that are presented in the Reversible and Irreversible inhibitor sections have not changed that much over the last 20 years. Furthermore I think these sections were well written and organized to begin with. Hence I don't think these sections require a comprehensive rewrite. The main problems with these two sections were lack of citations and jargon, but these has been fixed. Of course, if any additional issues are identified, I will work to correct them. Boghog (talk) 09:09, 26 June 2022 (UTC)

The article did a good job explaining what enzyme inhibitors do, but only in passing mentioned what they are. A new Structural classes section has now been added to provide a more complete description of what enzyme inhibitor are composed of (small molecules and proteins).Boghog (talk) 11:59, 12 July 2022 (UTC)

• Wikipedia does not seem to have anything to link to for clarifying cleave. Wiktionary has it as "splitting", while regular dictionaries have it as "adhering to". Which is the case here? Can a parenthetical be inserted on first occurrence of the word cleave? SandyGeorgia (Talk) 14:01, 12 July 2022 (UTC)

  Yes, "splitting" is correct. Jo-Jo Eumerus (talk) 14:04, 12 July 2022 (UTC)

  Thanks, parenthetical added. SandyGeorgia (Talk) 14:06, 12 July 2022 (UTC)

• Is repell BrEng? If so, can we add an inline comment so others won't change it? SandyGeorgia (Talk) 14:06, 12 July 2022 (UTC)

  That is a typo. It is spelled repel (wikt:repel) in both American and British English. Now fixed. Thanks for catching this. Boghog (talk) 09:24, 13 July 2022 (UTC)

  Struck, SandyGeorgia (Talk) 09:37, 13 July 2022 (UTC)

• The lead says AIDS, the body says HIV. SandyGeorgia (Talk) 14:15, 12 July 2022 (UTC)

  Fixed, struck. SandyGeorgia (Talk) 09:34, 13 July 2022 (UTC)

• Links to "sections above" won't work on Wikipedia mirrors, and need to be spelled out, as do things like "discussed above (where)? I have added inline queries. SandyGeorgia (Talk) 14:34, 12 July 2022 (UTC)

  See Wikipedia talk:Featured article review/Enzyme inhibitor/archive1, Samples of linking ... SandyGeorgia (Talk) 18:25, 13 July 2022 (UTC)

  Based on this suggestion, I have added internal wiki links between text that refer to imgages and the images themselves. Does this work? An alterative would be to include a figure number in each of the captions (figure 1, figure 2, etc.) and refer to the figure number. I cannot find any style guidline that would discourage this, but it does not seem to be widely practiced. Disadvantages of this aproach are maintenance and longer figure captions. Boghog (talk) 18:30, 13 July 2022 (UTC)

  See Wikipedia talk:Featured article review/Enzyme inhibitor/archive1 for alternate suggestion to use the title header on images, and refer to those. What is done now is a GREAT start, but doesn't work on Wikipedia mirrors. SandyGeorgia (Talk) 19:18, 13 July 2022 (UTC)

  Also, you can do a ctrl-f search on WHERE? to locate the other instances that need fixin'. SandyGeorgia (Talk) 19:25, 13 July 2022 (UTC)

  OK, thanks for the hint. I have removed all the links to images and replaced with reference to image headers. I have also searched for "see", "above", "below", and "right". Hopefully all references to images have been fixed. Boghog (talk) 20:27, 13 July 2022 (UTC)

  Much better ... I like it! But you still have to ctrl-f on WHERE? ... there are still several. SandyGeorgia (Talk) 20:39, 13 July 2022 (UTC)

  Missed your inline comments. Now working on it. Boghog (talk) 12:40, 14 July 2022 (UTC)

  Switched them so they will be easier to see [2] SandyGeorgia (Talk) 15:55, 14 July 2022 (UTC)

• Which dimer should be linked? SandyGeorgia (Talk) 14:37, 12 July 2022 (UTC)

  Done, struck. SandyGeorgia (Talk) 21:35, 12 July 2022 (UTC)

Noting my queries above, @Z1720, GamerPro64, and Hog Farm: for a new look. Jo-Jo Eumerus are you satisfied ? SandyGeorgia (Talk) 14:51, 12 July 2022 (UTC)

Sorry, it's summer and I have wound down my Wikipedia reading so I haven't done any deep reading here. Jo-Jo Eumerus (talk) 15:11, 12 July 2022 (UTC)

It's on the list for me. Although I should note that I'm not going to be very scientific-literate (my wife was shocked to find out that I don't know how many chromosomes a human has). Hog Farm _Talk 23:13, 12 July 2022 (UTC)

• MOS:COLOUR on the DFP reaction diagram; can it be redone to use a schematic other than color? See, for example, the maps at Great Fire of London. It should not be difficult to do that without dependence on color. SandyGeorgia (Talk) 18:38, 13 July 2022 (UTC)

  Technically challenging, but this may be a solution. I am working on it. Boghog (talk) 12:40, 14 July 2022 (UTC)

  Great! I would not hold up a FAC or FAR over this, but we should try to fix it when it's doable. SandyGeorgia (Talk) 15:56, 14 July 2022 (UTC)

  The lead image has been modified to add a checkerboard pattern to the inhibitor binding site. The substrate and inhibitor can be described by their shapes (rectangle and rounded rectangle respectively). The figure caption has also been modified to supplement the color legend with pattern/shape descriptions. I experimented with adding pattern to the substrate and inhibitor, but the results were not very aesthetic. Hopefully the shape descriptions are adequate. Boghog (talk) 15:45, 16 July 2022 (UTC)

This loses me:

• The binding of an inhibitor and its effect on the enzymatic activity are two distinctly different things, another problem the traditional equations fail to acknowledge. It is further assumed that noncompetitive inhibition results in 100% inhibition of the enzyme, and fails to consider the possibility of partial inhibition.

  "Two distinctly different"? --> ?? --> Another problem the traditional equations fail to acknowledge is that the binding of an inhibitor and its effect on the enzymatic activity are distinct.

  --> ?? The equations assume that noncompetitive inhibition results in 100% inhibition of the enzyme, and fail to account for partial inhibition.

SandyGeorgia (Talk) 05:14, 15 July 2022 (UTC)

• I agree that this was ackwardly worded. The general idea is that binding ≠ inhibition. Binding of a molecule to an enzyme does not guarantee it will inhibit, and if it does inhibit, the inhibition may be less than 100%, even if the enzyme is completely occupied by the inhibitor. I have edited this paragraph and hopefully it is now clearer. Boghog (talk) 11:02, 16 July 2022 (UTC)

This will not work on Wikipedia mirrors (which don't have Wikilinks); the "above" has to be explicitly named in text:

• Proteins can also be natural poisons or antinutrients, such as the trypsin inhibitors (discussed above) ... imagine the text without wikilinks, how does the reader know what is being referred to above?

SandyGeorgia (Talk) 05:17, 15 July 2022 (UTC)

• Replaced with a reference to the section heading name. Boghog (talk) 11:02, 16 July 2022 (UTC)

• Substrate is a dab: "The binding site of inhibitors on enzymes is most commonly the same site that binds the substrate of the enzyme." SandyGeorgia (Talk) 04:27, 16 July 2022 (UTC)

  fixed Boghog (talk) 11:02, 16 July 2022 (UTC)

Comments posted at Wikipedia talk:Featured article review/Enzyme inhibitor/archive1#HF. Hog Farm _Talk 04:42, 19 July 2022 (UTC)

Close w/o FARC, my concerns have been addressed. Hog Farm _Talk 13:20, 21 July 2022 (UTC)

• Close w/o FARC, thank you Boghog, and Hog Farm for the heavy lifting. Perhaps Graham Beards would have a look. GamerPro64 would you like to revisit? SandyGeorgia (Talk) 15:29, 21 July 2022 (UTC)

Many anti-viral drugs are enzyme inhibitors. The article mentions this indirectly in the lead but it is not followed up in the body. I think the article needs a paragraph on this. Graham Beards (talk) 17:52, 21 July 2022 (UTC)

See, I thought that many drugs period are enzyme inhibitors... Jo-Jo Eumerus (talk) 21:08, 21 July 2022 (UTC)

I can write the section if you agree. Graham Beards (talk) 22:13, 21 July 2022 (UTC)

I agree. I made a start. Feel to expand and edit. Boghog (talk) 12:59, 22 July 2022 (UTC)

I don't think we need much more. We should stress that the enzymes inhibited are mainly virus-encoded and not host ones. Also this citation, Kausar S, Said Khan F, Ishaq Mujeeb Ur Rehman M, Akram M, Riaz M, Rasool G, Hamid Khan A, Saleem I, Shamim S, Malik A (2021). "A review: Mechanism of action of antiviral drugs". International Journal of Immunopathology and Pharmacology. 35: 20587384211002621. doi:10.1177/20587384211002621. PMC 7975490. PMID 33726557. is not the best. It is poorly written, has numerous grammatical errors and is difficult even for me to understand. (Please forgive my immodesty). This one is much better: Bamford, Dennis; Zuckerman, Mark A. (2021). Encyclopedia of virology (4th ed.). Amsterdam. pp. 11, 129. ISBN 978-0-12-814516-6. OCLC 1240584737.{{cite book}}: CS1 maint: location missing publisher (link) - Graham Beards (talk) 15:47, 22 July 2022 (UTC)

Thanks for the suggestion. The Encyclopedia of Virology comes in five volumes and I tracked down the chapter "Antiviral Classification" starting on page 129 to volume 5. I agree it is a much better source and as a bonus, that chapter is freely available, so I have updated the source. What volume/chapter does page 11 refer to? Boghog (talk) 16:45, 22 July 2022 (UTC)

I don't know where I got "11" from. Graham Beards (talk) 17:02, 22 July 2022 (UTC)

OK, the "Antiviral Classification" chapter is sufficient. Boghog (talk) 19:02, 22 July 2022 (UTC)

Sorry for the late reply but I'm perfectly fine with closing without an FARC. GamerPro64 06:05, 31 July 2022 (UTC)

• Closing note: This removal candidate has been kept, but there may be a delay in bot processing of the close. Please leave the {{featured article review}} template in place on the talk page until the bot goes through. Nikkimaria (talk) 02:32, 6 August 2022 (UTC)

The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.