Wikipedia:Featured article candidates/Nicotinamide adenine dinucleotide

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

The article was promoted 16:46, 23 December 2007.

Nicotinamide adenine dinucleotide[edit]

Self nomination. An article on a central molecule in living cells, covering all major aspects from its properties, functions, pharmacology and history. Article was recently reviewed as a GA by a reviewer who encouraged me to put it forward as a FAC. It is 46 kb in size, containing 22 kb of readable text. Tim Vickers (talk) 23:22, 8 December 2007 (UTC)[reply]

  • Comment. As I think that a WP:Chem core article really deserves to be promoted to A-Class and preferably to FA, I won't deny yet. But no support yet either: there are quite some (solvable) problems with this this article still, where it doesn't comply with several WP standards. I left comments on the talk page. Wim van Dorst (Talk) 22:44, 9 December 2007 (UTC).[reply]
  • Comment, I talked to Professor Charles Brenner on the phone today (a researcher in the field) and he made some useful comments and caught some errors. I'll correct these this evening. Tim Vickers (talk) 21:02, 10 December 2007 (UTC)[reply]
  • Comments addressed were my use of the word "coenzyme" when NAD was being consumed as a substrate, missing out Jack Preiss and Philip Handler from the history, not defining mono and poly-ADP-ribosylation clearly, a new paper this October that shows a novel precursor for salvage pathways, and that the cytoplasmic concentration quoted only applied to animal cells not yeast. He also was unhappy with how certain I was about resveratrol's function, so I still have to reword that - I over-simplified that a little. Tim Vickers (talk) 19:25, 11 December 2007 (UTC)[reply]
  • Comments while I briefly poke my head in here again:
  • Does the 'DPN+' notation need to be mentioned in the lead? Not sure where else to put it, but the last sentence of the first paragraph seems like an odd place for such a tiny little nit.
  • Moved to chembox
  • 'concentrated in the cell nucleus, which may reflect the high level of ADP-ribosylation reactions in this organelle' - not quite sure which way around this goes. Sounds like you mean something like 'may be due to' instead of 'may reflect'; currently it sounds like the high level of ADP ribosylation is a cause rather than a consequence of the salvage enzymes' presence in the nucleus.
  • Changed to "which may compensate for the high level of ADP-ribosylation reactions in this organelle"
  • A better image of the NAD+ binding site illustrating the charge distribution would be nice. (I'm kind of embarrassed by the ugly perspective in the existing one!)
  • The image is pretty, but something Prof Brenner mentioned as well is that it would be better to get an image of NAD bound to a Rossmann fold protein. Perhaps some kind person might supply one?
  • Maybe I just missed it, but it would be nice to have a sentence mentioning the metabolic roles of NADP+/NADPH and how they differ from NAD+/NADH. Opabinia regalis (talk) 04:48, 11 December 2007 (UTC)[reply]
  • This is outlined at the end of the second paragraph of the "Role in redox metabolism" section - "In contrast, the main function of NADP+ is as a reducing agent in anabolism,..." Tim Vickers (talk) 16:46, 11 December 2007 (UTC)[reply]
I knew I must've missed it. Nice Rossmann fold too. Good work as always :) Opabinia regalis (talk) 06:55, 15 December 2007 (UTC)[reply]
Should've been clear that I meant that as a support. Opabinia regalis (talk) 06:01, 23 December 2007 (UTC)[reply]
  • Oppose now: Support- The article is not clearly enough about the one chemical compound NAD+. It introduces various other compounds every now and then in the article, and superfluous information (for this article) is provided. In my humble opinion the article needs better focus.
  • Hi there, thanks for the review. I think you are right that the article talked a bit too much about NADP+, I removed some of this. However, explaining what both NAD+ and NADH are is absolutely central to understanding what this molecule does in cells. Removing that information would greatly hinder a reader's ability to understand the subject of the article - the properties and functions of the coenzyme. We couldn't have one article on NAD and another on NADH, that would be unworkable. I have replaced some of the text you removed. Similarly, briefly contrasting the functions with the related coenzyme NADP (but I agree we shouldn't explain the functions of NADP in any detail, it has its own article) is important to show the reader how these two coenzymes differ - another vital concept.
  • The quality of the text is very varying. E.g., in the lead several very technical jargon terms are unexplained, whereas the simple chemical properties of redox agent are spread over multiple lines. This is also true for other places in the article.
  • I simplified the lead a little, the list of functions was a bit too long and technical. I changed this to a broad outline. Also shrank the redox function explanation.
  • Very straightforward indicators of compliance to WP guidelines, e.g. as by the peerreviewer script are not solved yet, e.g., British and English spelling are mixed, and I have the impression that the text hasn't been copy-edited for top-quality English.
  • As I noted on the comments page, the automated script is picking up UK English terms in the titles of a few of the references. I could change these to US English, but I don't think that is a good idea since that is not standard style and prevents the use of the titles as a search term. Tim Vickers (talk) 23:02, 15 December 2007 (UTC)[reply]
  • Sorry, but if that's it, I have to agree—changing reference titles would be like changing a direct quote. Unless you're say, italicizing an organism name or adding Greek characters, that's a bad, bad idea :) Fvasconcellos (t·c) 23:54, 15 December 2007 (UTC)[reply]
  • Ah, I misread the MoS and thought degC was unspaced, replaced the non-breaking space. You're quite right about that one. Tim Vickers (talk) 05:12, 16 December 2007 (UTC)[reply]
  • Bottomline, although Tim and others are giving the article good effort, it is GA-quality alright, but not FA quality. Wim van Dorst (Talk) 21:32, 15 December 2007 (UTC).[reply]
    • Since my last review above, the article has gone through excellent copy-editing (I'm glad to see in line with my proposals), touching on all of my objections. Therefore with pleasure I change my feedback from Oppose to Support. This is now the required quality. Wim van Dorst (Talk) 15:47, 23 December 2007 (UTC).[reply]
  • Some comments. The term 1' should probably be explained, or written in prose, as I don't know what the ' stands for. The prose could be better; living things (things is one of those words that should be avoided; try organisms), NADP+ since in NADP+ (try and reword to avoid the redundancy). Some sources are needed (I'm a little eccentric about it); at the end of the first paragraph in Physical and chemical properties, the end of the second paragraph in Salvage pathways, the end of the first paragraph in Oxidoreductases, and the end of the first paragraph in Pharmacology. Most are probably sourced in other references, but I like knowing that every last statement is sourced. --Hurricanehink (talk) 06:00, 16 December 2007 (UTC)[reply]
Hi there, thanks for the review.
  • 1' now defined and linked
  • Repetitive sentence removed, it was a bit off-topic anyway, as noted above.
  • Replaced with "organisms"
  • Refs added to all but last, which is a summary of the paragraphs below and isn't in a single reference, but describes what the topics of the other sections are. I've reworded this a bit to make it clearer. Tim Vickers (talk) 06:39, 16 December 2007 (UTC)[reply]
  • Cool. Alright, I gave it another look through, and it does seem very technical, to the point that Wikilinks doesn't help too much for the reader to understand the article. At the same time, there are some vernacular phrases in there (from scratch) and it wanders a bit (from the diet - no reference to what that diet is before then). I don't believe it passes criterion 1a. Perhaps you could get a look-through from another editor in your WikiProject? --Hurricanehink (talk) 17:18, 16 December 2007 (UTC)[reply]
  • I reworded "from the diet" into "taken up from food as vitamins", which is more precise and probably a bit clearer. I know this is rather a technical subject, what I will try to do is re-write the lead so it it completely approachable to those with no background in the subject, have another run-through to remove unnecessary technical terms, and add a summary sentence to the start of each section that gives a non-technical overview of the contents. Tim Vickers (talk) 18:46, 16 December 2007 (UTC)[reply]
  • CommentSupport 1) Why abbreviate as NaAD etc instead of NAAD? 2) There is nothing about transport of NAD between compartments, e.g. can NADH from the citric acid cycle be used by enzymes in the cytosol? Narayanese (talk) 09:14, 16 December 2007 (UTC)[reply]
  1. I don't know why people use Na and NaAD, but this is the standard in the literature (see diagram p14 of Belenky review), so I chose to follow, rather than lead!
Following convention is good. Narayanese (talk) 19:30, 16 December 2007 (UTC)[reply]
  1. The glycerol phosphate shuttle is mentioned in the latter part of the first paragraph in the "Role in redox metabolism" section. Do you think this should be expanded? Tim Vickers (talk) 17:16, 16 December 2007 (UTC)[reply]
Ok, now I see the sentence. Took a while to understand the Glycerol phosphate shuttle stub btw, but I get the idea it doesn't involve matrix NAD, it is probably that article that needs work eventually rather than the NAD one. Can it go the other way (CAC->gluconeogenesis?). So NAD can't pass the membrane itself, so how does it get to be in other organelles than the nucleus, is the synthesis pathways present in all organelles?
The articles mention measuring NAD in the cytoplasm and then talks about other compartments, does it perhaps mean cytosol? Narayanese (talk) 19:30, 16 December 2007 (UTC)[reply]
  • Good point, I only mentioned one of the shuttles. I added a link to the general article on mitochondrial shuttles, and a specific link the the malate-aspartate shuttle, which is the better one of the two daughter articles.
  • There is very little published on organellar NAD transport/biosynthesis apart from that nuclear localisation paper I found earlier, but I found and added an article stating that the shuttle systems also work in chloroplasts and a paper on NAD import carrier in mitochondria.
  • The term should be cytosol, good catch I always get those confused. Tim Vickers (talk) 19:56, 16 December 2007 (UTC)[reply]
Looks like you've fixed the points nicely. In these two sentences "NAD+ absorbs strongly in the ultraviolet due to the adenine base. Peak absorption is at a wavelength of 259 nanometers (nm), with an extinction coefficient of 16,900 M-1 cm-1. The reduced form, NADH, also absorbs at a higher wavelength, with a second peak in UV absorption at 339 nm that has an extinction coefficient of 6,220 M-1 cm-1." I'd suggest you put a sentence/clause with the extinction coefficient of NADH at 259 nm between the two. Atm the second hangs in the air, and it is not understood why NADH is preferred for measurement.
Does the Rossmann fold always use /drastic/ induced fit for NAD (should be mentioned if it does, at either page, otherwise unimportant)?(confused with a non-Rossmann fold-containing oxidoreductase) sidenote: you might want move a bit of the text to Rossmann fold, specifically the FMN sentence.
I can't spot any grammatical or spelling mistakes, and all non-trivial text is referenced to scientific databases and journals. Narayanese (talk) 22:42, 16 December 2007 (UTC)[reply]
I reworded that piece about the absorbance coefficients and cut the FMN sentence. Tim Vickers (talk) 03:02, 17 December 2007 (UTC)[reply]
Ok, good.
The article has nothing important omitted, no overrepresented minority beliefs, lead has the most important from each section, good section and paragraph splitting and headings, ilustrations without copyright issues, medium length. It's ready for FA status as far as I can see. Narayanese (talk) 06:07, 17 December 2007 (UTC)[reply]

Oppose for now, but it's almost there. -- Changed to support'. All of my concerns regarding content have been addressed. I think the article still needs some copyediting (I just fixed a typo for "conezyme") but I see it is undergoing vigorous editing to improve these details. If I find any other typos or similar errors I'll just fix them myself. One final comment: I don't think it was necessary to completely remove the 3D image, although I do prefer the 2D structural diagram at the top of the infobox. --Itub (talk) 12:00, 21 December 2007 (UTC)[reply]

  • The main problem is that the prose doesn't feel right at places. There are some awkward and sometimes even ambiguous sentences in places, especially near the beginning of the article, and even some grammar errors such as lack of subject–verb agreement. I don't have time to elaborate right now, so I'll understand if this is considered a non-actionable objection for now.
  • Probably due to the large edits that keep being made to the lead. Will work on this a bit more.
  • Leas has now been re-written again for simplicity.
  • The structure. IMO, it would be better to show the structural diagram first, and the 3D figure later. Structure diagrams are more readable since they avoid the problem of overlapping atoms. For example, the top ribose ring in the 3D figure is a jumble that won't be intelligible to anyone who doesn't know the structure already (this is not a complaint against the author, as it is often impossible to find a perspective with no overlapping atoms).
  • This was a conscious decision. I thought it might be best to put the structural diagram next to the text that discussed the details of the structure, which is at the top of the first section, so tat readers could refer to it as they read the description. Originally, the two figures were revered. Do you think the structural diagram would be best next to the lead?

Another problem with the 3D figure is that both phosphates are protonated, which not only is unlikely under most conditions but is inconsistent with the structure diagram, which could lead to confusion. Finally (and that is often a problem with 3D structure representations in Wikipedia), it would be good to clarify exactly what this structure is depicting. Does it come from a crystal structure? (In that case, the crystal of the pure substance, or bound to something?) Is it supposed to be the global energy minimum conformation according to some model, under some conditions? Or is in just an arbitrary conformation chosen for artistic purposes?

  • I've left a note with the author of this image and asked if they could respond here.
I'm the author of the image. The phosphates are protonated because it's simpler than to try and represent every possible protonation state that could occur in vivo.
The structure is not from x-ray diffraction, it's just a local conformational minimum, chosen mainly to make the structure as clearly visible as possible. As mentioned above, it is extremely difficult, often impossible, to present a 3D model of a molecule in 2D in such a way that no atoms are obscured. I did my best with this image.
I didn't bother finding a crystal structure for this molecule because it does all its important chemistry in solution or bound to proteins, so its conformation in the bulk pure solid doesn't necessarily reflect its conformation in a cell.
I'm happy to modify the image as required, won't be a problem. Decide what you want from a 3D model, let me know, and I'll make it.
Ben (talk) 15:48, 17 December 2007 (UTC)[reply]
  • This £D image has now been replaced with the structurral diagram. Tim Vickers (talk) 10:43, 21 December 2007 (UTC)[reply]
There should be a 3D model, though, because the structural diagram gives very little indication of the shape of the NADH molecule. Massively distorted P-O bonds and so on!
I could use PDB 2FM3.
Ben (talk) 16:52, 21 December 2007 (UTC)[reply]
  • OK, that sounds like a good option. Attractive and informative images are very welcome. Thank you. Tim Vickers (talk) 11:16, 22 December 2007 (UTC)[reply]
  • The UV spectrum. I find it hard to believe that the absorption maximum wavelength and the extinction coefficient are exactly the same for NAD+ and NADH. To help more visual readers it would be helpful to include a figure of the UV spectra, such as the one in this book [1]. (The extinction coefficients look different in this figure).
  • I've reworded this to make it clear that I was using NAD+ as the specific example. A free verion of this diagram would be good, I considered just recording them myself, but this might be considered OR and it's always hard to get the concentrations exactly right, so the isobestic points and maxima would probably be wrong. I could draw one feehand, but that wouldn't be very accurate either. Tim Vickers (talk) 15:04, 17 December 2007 (UTC)[reply]
  • I grabbed the data from the book you linked to and made a new version while I was stuck on a transatlantic flight. This has been added to the article. This involved re-arranging the images and removing the 3D version.
  • Reduction potential. Given that the most notable property of this molecule is its redox nature, I find it is a major omission not to include the standard reduction potential in the article. Perhaps compare it NADP+ and other relevant species to put it in context. Maybe it would be worth explaining it more detail how the oxidized/reduced ratios of NAD+ and NADP+ are regulated.
  • Good point! A serious omission. Will track it down this afternoon.
  • Added midpoint potential with reference and sentence on NADH being strong reducing agent to give context.
  • Niacin. Sometimes the article talks about niacin and sometimes about nicotinic acid. Yet, at least according to the article on niacin, they are one and the same. Or does niacin (still) refers to a mixture containing nicotinic acid and nicotinamide, as the History section states? In any case, this should be clarified.
  • It is a mixture of the Na and Nam, but not NR, so "niacin" refers to two of the three NAD+ precursors in our diet. This does ned to be explained a bit better. Tim Vickers (talk) 14:54, 17 December 2007 (UTC)[reply]
  • Now mentioed in lead and explained in full in salvage pathway section. Tim Vickers (talk) 10:43, 21 December 2007 (UTC)[reply]

Hope this helps. --Itub (talk) 10:21, 17 December 2007 (UTC)[reply]

  • Object per lacking quality of writing in lead. "peacock" lack of organization- audience is general reader and it is not well written imo in reference to that--Keerllston 12:25, 20 December 2007 (UTC)[reply]
  • Hi there, I'm a bit confused by your comment. Which "peacock" terms are used in the lead? The only one I can think might apply is the statement that the coenzyme is very important and thus a target for drug discovery, this was a paraphrase of the review PMID 17465726, so can be referenced if required. Tim Vickers (talk) 09:51, 21 December 2007 (UTC)[reply]
  • The first part of the lead has now been expanded to give a less technical explanation of redox reactions. Tim Vickers (talk) 10:49, 21 December 2007 (UTC)[reply]
  • I'm confused by the previous reviewer's rationale for objecting. It seems to be a fine piece at first glance: I'll look carefully at it soon. Tony (talk) 13:51, 21 December 2007 (UTC)[reply]
The above discussion is preserved as an archive. Please do not modify it. Subsequent comments should be made on the article's talk page or in Wikipedia talk:Featured article candidates. No further edits should be made to this page.
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