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)

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
 * *Ki, enzyme inhibition

which is clearly contrary to MoSDab bcz of the piping, i put instead
 * Ki, symbol for effectiveness of enzyme inhibitor

with "symbol for" as a shot in the dark. It's still not acceptable, bcz Ki (AFAI can see) the article isn't on Ki, Ki doesn't even get mentioned above the third heading (4 screens down from the top of the page), AFAI can see Ki 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 Km." 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? — Æµ§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. Sandy Georgia (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)