Wikipedia:Peer review/Enzyme kinetics/archive2

Enzyme kinetics[edit]

Hi there. This article has been comprehensively re-worked over the last few weeks. I'm hoping to bring it up to FA status and suggestions to help this would be much appreciated. Previous peer-review TimVickers 18:42, 25 September 2006 (UTC)[reply]

This article has now been nominated for FA, any futher suggestions should be added to its candidacy page here. Thank you. TimVickers 20:43, 28 September 2006 (UTC)[reply]

This is an interesting article, although it rapidly gets quite technical in places. Here are a few (hopefully useful) comments:

The word catalysis should be linked in the first paragraph, as this is a key concept.

Good point, done.

I know the second paragraph of the introduction is trying to explain how enzymes operate, I think it could be improved by some reordering. For example, "Enzymes are molecular machines that manipulate specific molecules: their substrates. These target molecules bind to an enzyme's active site and then are transformed into a product. In order to gain a complete picture of how enzymes work, we need to know both their structures and their mechanisms. An enzyme's structure is akin to a complete blueprint of one of these machines. The operating mechanism is provided by chemical kinetics; similar to a movie of this machine in action." Although I'm sure that can be improved.

Good, added.

In the "Enzyme assays" section, what are products and reactants? Are the reactants the enzymes and their substrates?

Tried to clarify.

Could you clarify the statement, "polypeptide chain that report movements during catalysis"? It is not explained prior to that point.

Removed the word "polypeptide" and generalised this a bit.

The section "General principles" states that "shows if an enzyme can catalyse a reaction under the conditions in the cell". But doesn't the enzyme always catalyze a reaction? Perhaps this could be clarified.

Reworded.

In the first illustration of the single-substrate reactions section, should the (S) be [S]?

Confusing, reworded.

So my issue here remains, albeit a very minor point. The caption on the illustration uses "(S)" and defines it as the "concentration of substrate". The surrounding text uses [S], and defines it as "substrate concentrations". These appear to be identical, so I would be expecting the caption to be using [S] also. Thanks! :-) — RJH (talk) 18:31, 29 September 2006 (UTC)[reply]

I was trying to introduce the abbreviation S as standing for substrate and had put it in parenthases. I've removed it entirely and I think this solves the confusion. TimVickers 14:44, 30 September 2006 (UTC)[reply]

I'd like it if the first two equations were separated out from the text. Could each of the equations be indented? Also what is k₃? it is not mentioned in the second illustration.

Good catch, k2 is correct. Indented equations.

I think there should be a period after "the expression reduces to Km = [S]".

OK, these were missing in a couple of places.

Could you clarify this sentence: "In these enzymes both substrates bind to at the same time to produce an EAB ternary complex"?

Urgh. What an ugly sentence. It's better now.

"...E* by for example transferring..." needs commas around "for example".

Added.

Intermediates should be linked where it first appears in the text.

Linked and defined.

Can interconversion be explained?

Replaced with "Consumption"

In the "Enzyme inhibition" section, a brief explanation of the term would be useful, as would the meaning of "reversible" in this context. (Rather than leaving it to the Enzyme inhibitor article.)

Defined terms.

Likewise the listed types of inhibition should probably also be explained, since they are used in a table.

They are defined in kinetic terms in the table and diagram, and I've now listed them in the text as well.

Thanks. — RJH (talk) 21:59, 25 September 2006 (UTC)[reply]

Hi Tim,

the article lacks any mention of ordered sequential mechanisms for two substrate enzymes, a common (maybe just to me?) two substrate mechanism. I'll get to work writing one up, can you provide diagrams? that way they will be consistent with the others on the page. NB: ordered sequential is E + A → EA → EAB → EPQ → EP → E, where the binding order of A and B, and the release order of P and Q must happen in order. typically happens in tunnel-like active sites, where binding of the second substrate blocks access to the first. Xcomradex 22:23, 25 September 2006 (UTC)[reply]

oh wait i see it mentioned briefly in the ternary section. probably needs expansion anyway. Xcomradex 22:29, 25 September 2006 (UTC)[reply]

Tim, you've done an awesome job on these enzyme articles. A few nitpicks for this one:

Is reaction mechanism wikilinked anywhere?

Added to introduction.

The phrase "are transformed into a product" sounds a little oversimplified, though I'm not coming up with an improvement.

Should be plural, it is wrong in singular.

There are a couple of minor tone problems: "we need to know...", "lets you measure...", etc.

Fixed later one, intro is deliberately non-formal so general reader isn't scared off immediately!

It seems a little odd that "general principles" comes after the assay section. Also, this sentence - "Knowing these properties shows if an enzyme can use this substrate under the conditions in the cell, and if it does, how important this activity is compared to any other enzymes that may perform the same reaction" - is a little awkward; it doesn't seem like the most common situation - bad substrates are often unnatural, and an enzyme's level of activity relative to similar enzymes doesn't necessarily correlate to importance (maybe it's a lousy whateverase, but it's the only one in mitochondria). Maybe something more general like "Knowing these properties about an enzyme helps in determining its cellular function"?

Sections re-ordered. Section reworded.

Image:Enzyme saturation.png only has 4 out of 5 enzymes bound to substrate - sure, at high concentrations there will be times when that's the case, but as an illustration of "saturation" it might be more effective to see them all filled.

My bad. Altered diagram.

Does the Michaelis-Menten kinetics section need a main article tag? Then you could avoid the "to see a full derivation" reference. Also, "Practical significance of kinetics" is kind of stubby.

Tag added, practical significance is new today, so still work in progress.

Image:Mechanism_plus_rates.svg and the related discussion assumes that the slow step is the catalysis rather than the binding - it would be good to specify that. I'd have to dig but I'm sure there are examples where it's the other way around.

There are such examples, but I don't think they follow simple MM kinetics. I'll do some reading on this and see if there is a way of including them.

I think you're right, the only example I can think of is unclamped DNA polymerase, and that's not MM. Opabinia regalis 01:52, 28 September 2006 (UTC)[reply]

Paragraph about Briggs-Haldane kinetics now added. TimVickers 20:12, 28 September 2006 (UTC)[reply]

The ternary complex section doesn't make a distinction between EAB->EPB->EPQ and EAB->EAQ->EPQ. I'm not sure if that's within the resolution of experimental methods, but it seems like there must be a couple of examples where one reaction is fast and one is much slower.

Almost always in these reactions either A turns to P producing E* and then B is changed to Q (ping-pong) or A and B react with each other in the active site (ternary complex).

I see a weird artifact where the ping-pong section's edit link appears on top of the text "This link is" in the last sentence - maybe the ping-pong image needs to move down a bit.

Moved image, did this change anything?

Looks better now. Opabinia regalis 01:52, 28 September 2006 (UTC)[reply]

If I were going to add something to this article, I'd add more discussion of the structural bases for cooperativity. It would be great to see a structure where ligand binding at one site opens or blocks access to the other, if you can think of any likely examples.
"Often, the detection of an intermediate is essential in proving what mechanism an enzyme follows." - I had it hammered into me by a particularly hard-headed empiricist that you can't prove a mechanism, you can only discount alternatives. Maybe a nitpicky point but I can't help it.

OK, rephrased.

Thanks for all these suggestions, will keep me busy for days!

Opabinia regalis 00:35, 27 September 2006 (UTC)[reply]

Hi Tim, thanks for your call to this PR. Feel free to rally me again once the document has been spell-checked. Kind regards, Samsara (talk • contribs) 08:34, 27 September 2006 (UTC)[reply]

Thank you for the advice. I found the spelling mistake you refer to and have fixed it. TimVickers 14:46, 27 September 2006 (UTC)[reply]

Thanks. I don't have much time just now, but this poked my eye:

To experiment with the Michaelis-Menten equation, there is an interactive Michaelis-Menten Kinetics tutorial.

This should probably be rephrased so that it still makes sense when seen offline or in print. The link should not be the motivation for the sentence, it should be supplementary. Otherwise it can go in "external links". - Samsara (talk • contribs) 15:31, 27 September 2006 (UTC)[reply]

Thank you, I hadn't considered this. Moved reworded link to end of sentence. TimVickers 15:47, 27 September 2006 (UTC)[reply]

This is interesting. In a GA nomination I was told it was better to integrate external links into the surrounding prose for readability, and I took the suggestion; I hadn't thought about offline or print readers then having useless sentences lying around. Anyone know of any data on how ofter people use Wikipedia that way? Opabinia regalis 01:52, 28 September 2006 (UTC)[reply]

Can you remember who made that suggestion? I'm intrigued... No idea on print distribution, sorry! I could speculate that some teachers may print articles for their pupils. I can also see how integrating the links may benefit a short article more than a longer one, but your GA may well have been long... - Samsara (talk • contribs) 09:00, 28 September 2006 (UTC)[reply]

The reviewer was NCurse, and the article was multiple sequence alignment, which isn't especially short. In that case I put the links on the names of the software tools I was linking to, so it didn't produce too many odd-sounding sentences, but I wonder how consistent this suggestion is. Opabinia regalis 00:45, 29 September 2006 (UTC)[reply]

I see. My interpretation is that that's routinely done for things that don't yet have an article, but should. Others use the notation BLOCKS [1], which may be less aesthetically pleasing than your solution. - Samsara (talk • contribs) 07:13, 29 September 2006 (UTC)[reply]