Talk:Hemocyanin
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This article states that hemocyanins differ from hemoglobins in that they do not bind oxygen co-operatively. On the contrary, many hemocyanins are extremely co-operative, in fact, many are much more co-operative than most hemoglobins. Some are the most co-operative binding proteins known. The conformation changes that accompany the increased (and sometimes decreased!) oxygen affinity as oxygen binds to these very large multisubunit proteins is at least partially known for some hemocyanins. Also hemocyanins may respond to other allosteric effectors in addition to oxygen
Also the statement that hemocyanins bind oxygen with one-fourth the effeciency of hemoglobin is misleading. A single polypeptide subunit of hemocyanin binds one molecule of oxygen, as does one polypeptide subunit of hemoglobin. Vertebrate hemoglobins are made of 4 polypeptides; arthropod hemocyanins are made of at least 6 polypeptides and can have up to 48. Thus a single arthropod hemocyanin can carry 6 to 48 molecules of oxygen since they have 6-48 subunits, 1.5 - 12 times the number of oxygen molecules carried by a typical vertebrate hemoglobin.
(See van Holde, K.E., and K.I. Miller, 1995, Hemocyanin, Academic Press, NY.) --67.84.174.97 21:21, 15 August 2005 (UTC)
If you can state the mechanism (or at least theorized mechanism) for cooperative binding of hemocyanin be it by telecommunitive confirmation changes, allostaric inducers, ect that produces as oxygen binding dissociation curve that is equal to or superior to hemoglobin, please do so, that would be great. Here is a article (by van Holde, K.E., KI Miller, van Olden E. 2000 Aug 30,Biophys Chem. 86(2-3):165-72.) That seems to state the opposite to your claim. "In contrast to small allosteric systems (like hemoglobin) those containing very large numbers (n) of binding sites never exhibit cooperativity (as measured by the Hill coefficient, nH) even approaching the potential limit, n." --BerserkerBen 21:21, 15 August 2005 (UTC)
Efficiency is roughly based on the amount of oxygen release and up-taken per amount of blood (it might be better to use the word “effectiveness” instead), this is usually dependent on the dissociation curve and oxygen partial pressures of arterial, capillary and venereal blood, Although pH and other allosteric inducers levels can have significant impact on this. Here a article (Makino N. J Biochem (Tokyo). 1989 Sep;106(3):423-9.) that states a Hill coefficient 1.6-1.7 for the Hemocyanin from Tachypleus gigas. This is the highest I can find amoung articles of hemocyanin with stated Hill coefficients, many of which state coefficients of 1 or less. Hemoglobin has a coefficient of 2.8. Hemocyanin from Tachypleus gigas. Does show significant cooperatively and that should be stated, another article also seems to show a mechanism for this cooperatively and that should definitely be stated as well, thank you for bring these corrections to note.--BerserkerBen 21:21, 15 August 2005 (UTC)
Let us be clear here. Cooperativity is not a measure of whether one oxygen carrying blood pigment is superior or inferior to another. Many factors (too many to be discussed here) determine how well oxygen carriers function to deliver oxygen from the respiratory surface to body cells (see: Burggren, W., McMahon, D. Powers. 1991. Respiratory functions of blood. In: Environmental and Metabollic Animal Physiology: Comparative Animal Physiology. 4th ed. C.L Prosser. ed. Wiley-Liss. NY. pp. 437-508.) In fact, though most hemocyanins (Hc’s) bind oxygen co-operatively, they generally do not function as well as many hemoglobins (Hb’s). This is mostly due to the fact that Hb’s may be found in red blood cells, thus the blood may contain very high concentrations of Hb without adversely effecting the overall osmolality of the blood plasma. Hc’s are always extracellular, thus the maximum blood concentration is limited by the maximum allowable tonicity. Hence, the oxygen carrying capacity of blood with the oxygen binding pigment contained in cells (many but not all Hb’s, esp. vertebrate Hb’s) can be much higher than blood where the binding pigment is dissolved in the plasma (all Hc’s). This problem is only partially compensated by the fact that each Hc molecule can carry 1.5-12 times the amount of oxygen as a single vertebrate Hb molecule.
In the quote above Van Holde et al. state that co-operativity of very large allosteric systems (like Hc’s) never approach the number of total number binding sites as occurs in smaller systems (like vertebrate Hb’s). He goes on to say: The reason for this appears to be that in such macromolecules the cooperative unit always represents some sub-structure of the entire structure. (He was also including the molluscan extracellular Hb’s as examples of very large allosteric systems.) In the case of arthropod Hc’s, the function unit is a hexamer (six polypeptide subunits, each with one oxygen binding site). Larger Hc’s are made of 2, 4, or 8 of these hexamers. Thus the maximum possible Hill coeffecient (nH) for arthropod Hc’s is 6, even in the case of Hc’s with 48 binding sites. For example: the Hc from the Dungeness crab (one- and two-hexamer Hc’s) has a Hill coefficient of 3-4 depending on pH and other allosteric effectors like lactate (Graham et. al. 1983. Comp. Biochem. Physiol. 74A: 45-50). (The nH value is so high that the Hc does not work very well to deliver oxygen under normal conditions!) Molluscan Hc’s (which have a different subunit organization than arthropod Hc’s) can have Hill coefficients exceeding 6! (van Hold, K.E., and K.I. Miller. 1985. Haemocyanins. Q. Rev. Biophys. 15: 1-129). For comparason: some molluscan extracellular hemoglobins can also have Hill coefficients as high as 6 (van Hold, K.E., and K.I. Miller. 1985. Haemocyanins. Q. Rev. Biophys. 15: 1-129), As noted above, most mammalian Hb’s have Hill coefficients of about 2.8, Other vertebrate Hb’s may have other values. The theoretical maximum value of nH for vertebrate Hb’s is 4 since vertebrate Hb’s are composed of 4 polypeptide chains containing one oxygen binding site each.
Also strickly speaking oxygen binding curves like the one shown are not logarithmic. That curve is sigmoidal, non-cooperative binding curves are hyperbolic. In neither case is the curve logarithmic. Hb's and Hc's both may show co-operativity.
In summary: Hc's are very large oxygen binding proteins. The oxygen binding site contains copper, and Hc's are exclusively extracellular. Hb's are generally smaller (but some can be be quite large), the oxygen binding site contains an iron atom, Most Hc's are contained in red blood cells, but some invertebrate Hb's are found dissolved in plasma. Hb's and Hc's both may show cooperative oxygen binding and allosteric responses to a variety of effectors. The ranges of cooperativety shown by these two classes of oxygen binding proteins are very similar. Some very large extracellular molluscan Hb's and Hc's can have nH values as high as 6, though the nH of most Hc's and Hb's are much lower than that. Vertebrate, tetrameric Hb's have nH values of 2.8 - 4. Since all Hc's are extracellular, the total oxygen carrying capacity of Hc containing blood is much lower than blood containing intracellular Hb's, but in general similar to blood with extracellular Hb's.
PS. You mean venous, not venereal!--
Well you can nit pick all you want: Hyperbolic and logrithimic look the same, I even see it described as "rectangular corned", ect, I don't care. This is not an Internet forum for debating or showing off, it is the quality of the article that counts and I advice you to add and correct it. A few things though: I would prefer you try to state natural coefficients on the article, not coefficients gathered in conditions not meant to emulate their biological environments. Don't complain about grammar and spelling errors, I make a lot of them, and wiki in general is full of them, just edit them if you spot them. Also dumb it down or link any large words when you contribute to an article, wiki is meant for the laymen. Beside etiquette read the rules before contributing. Most of all join our community by registering; I look forward to your contributions. --BerserkerBen 21:42, 16 August 2005 (UTC)
Sorry, I did not mean to offend anyone. Yes, I should have registered and edited the hemocyanin page. As you guessed I am new to Wikipedia and was uncomfortable doing a major rewrite of an entry. I will do that edit when I can find the time. It requires major editing, thus requires a large time investment. It is full of important factual errors that are completely inconsistant with the very large scientific liturature on these very interesting proteins. (Do a PubMed or Google Scholar search for reviews by Terwilliger, Mangum, Bridges, or van Holde.)
For example: arthropod hemocyanins are always hexamers (six polypeptides), never dimers (two polypeptides). There is no such thing as an arthropod hemocyanin with only two subunits. But the circulating molecule may be this hexamer, or aggregates of the hexamer (2, 4 or 8 hexamers). The two-hexamer is often casually refered to as a dimer (a dimer of hexamers, note: the 4 hexamer is a dimer of two-hexamers, and the 8 hexamer is a dimer of 4 hexamers), thus the confusion shown in the article. Also, most arthropod hemocyanins have far more than 2 different kinds of subunits. For example, the Dungeness crab has 6 different subunits, blue crabs about that many. Interestingly, the subunit composition may change with development (Dungeness crab) and/or environment (Blue crab) or may stay constant, depending on the species. (I will provide references in the edit.) Unlike the well described Hb's the functional role of this subunit heterogeneity of Hc's is not well understood.
Molluscan Hc's do not show the dimer of hexamer structures as do arthropod Hc's. So their structure needs to be discussed separately. Interestingly, like the hemocyanins seen in arthropods and molluscs, molluscan and arthropod hemoglobins are often found dissolved in plasma. These molecules can be huge; much, much larger than the typical tetrameric vertebrate hemoglobins. Thus hemoglobins are not necessarily all intercellular, though most are and all vertebrate hemoglobins are. Hc's are never found in cells.
What do you mean you don't have time??? Your wrote the above dissertation didn't you? If you had time to do that you could have done it in the article and not the discussion! With 5-10min tops you could modify and integrate that into the article right now! What offends me is that you haven’t modified the article yet! Look you can just spend 5-10mins a day changing it slowly, most articles evolve not metamorphosis, surely you can do that?--BerserkerBen 22:57, 18 August 2005 (UTC)
Yes, I could edit the page in 5 minutes, and it would be full of missrecalled facts and misinformation as the page is now. I have been out of the field for a while, facts have to be checked, references looked up and checked, and proper citations made (as requested by Wikipedia), Getting one's facts right is not a trivial matter. For example, molluscan hemocyanins are now lumped with arthropod Hc's (or actually no distinction is made at all). In order to correct that I will have to do the research (my expertise is the arthropod Hc's). That will take some time.--
You mean getting the "details" right, not "facts". Facts are something of a higher order then a article on a free web based encyclopedia. Details can be made generalized enough that they are true most of the time, and the exceptions can be noted briefly, for example you can say: "Mollusk and Arthropod hemocyanins are relatively distinct from each other with significant differences in primary, secondary and tertiary structure, Mollusk usually... Arthropods usually... some exceptions are..." get the idea? This is not a textbook or a secondary source, it would be great if it did have such a level of quality, but we don’t ask you for that, we ask you for general details and overviews and over time the adding in of more specific details at what ever rate you wish, all the while maintaining article readablity. So stop thinking peer review article and start thinking basic explanation to a guy on a bus (or a moose in a room LOL). --BerserkerBen 03:04, 19 August 2005 (UTC)
Facts are facts, and the devil is in the details. Arthropod hemocyanins are never dimers, that's a fact, thus that statement in the page is flatly false and should not be there, period, end of discussion. The problem with that page is that there are so many errors of this sort, that it is fundamentally misleading.
You are obviously interested in Hc's. That is why I suggested the review articles. Rather than argue with me why not learn more about these interesting proteins so you can get your facts right. A full text review by van Holde is available here. Note the example of an arthropod Hc for which he has a nice illustration has 7 different subunit types. He also has nice illlustrations of the differences between molluscan and arthropod Hc's. Note: the illustration in the article is of a hemocyanin functional unit - not the whole hemocyanin. So again the legend to that illustration was fundamentally misleading. It shows a molecule over an order of magnitude smaller than a circulating Hc. Hc's are huge especially molluscan Hc's. That illustration does did not show that. I did edit the legend to reflect those facts.
This discussion is getting personal and silly. The Hc page has far too many serious errors of fundamentally important facts: from the molecular weights of the subunits (facts), number of subunits in the functional units (facts), to the nature of the cooperativity (facts), etc. The good Wikipedia pages have enough general information to satisfy the general reader as well as enough detail to satisfy the more technically oriented. Look at the Wikipidia pages for sigmoidal or hemoglobin, for example. To edit the Hc page that is both factually correct and useful to a broad range of readers, will require some care and time. Most of the pages I have visited on Wikipedia show this care (or have evolved to show this care). At the moment the Hc page does not; it is too flawed for quick fixes, I tried that and could not make the page work. --
Really, I see dimmer forms on pubmed, and I also already noted a usual size of hemocyanin in the article. Even if no scientific research does stated a oligomer arrangement of dimers, that does not mean it does not exist, if it were found then what you call a fact would infact have been erronous! Facts are an impossiblity, everything is theory! Stating things as "facts" opens your self to the possiblity of being disproven, to haveing stated data the becomes outdated, generalizations are much harder to disprove. I'm not really interested in hemocyanin, rather I started from the hemoglobin site and notice that we needed better coverage on other oxygen binders. I have no problem with you fixing errors or seeking perfection, but you said you had major time constraints, which will make your goals very difficult, so I suggested generality and evolutionary editing, almost all pages started like this, check out the history of hemoglobin and sigmoidal and look at their first versions, corrections and additions was a slow processes taking years. I don't feel this is getting personal (at least for me), silly yes... that because that is who I am. :-)
Also could you signature your entries, it would make it easier to read through, hit the sig. button at top, it will make two "-" and four "~": then when complied will make something like this: --BerserkerBen 03:14, 20 August 2005 (UTC)
Thanks for the info on how to signature the entries. I am still learning how all this works. I am glad this is not getting personal. So now we can get this page in shape. Perhaps, it should be shortened, with few details until we can get those details right, over some time. I will do my part and plug away on it.
Now I see where the confusion is coming from. You are going to have to get into the papers, rather than just reading the abstracts. Abstracts rarely have the details you need. That is where you got into trouble with the low nH values, and numbers of different kinds of subunits, molecular wts., etc. Often those numbers are only mentioned in the abstracts when they diverge from the normal values seen elsewhere in the liturature!!
Also abstract often use language understood by workers in the field, but not by outsiders (that's a real problem with abstracts.) So PubMed does make reference to dimers but these dimers are not dimers of single polypeptides. In the arthropod hemocynanins those dimers are dimers of hexamers!! Those two-hexamers (24mers) may also form dimers to make 48mers. The circulating Hc's may be the hexamer, 24mer (dimer of hexamers), 48mer (dimers of dimers of hexamers) or combinations of these, never, ever a dimer of two polypeptides (such dimers would not work to transport O2). This hierarchy is unique to arthropod Hc'a as as I know. van Holde's review (full text online) explains this hierarchy and has a good figure showing it.
The molluscan Hc's have a completely different hierarchy. The subunit is enormous 350-450 kDa consisting of 7-8 functional units (your illustration) connected by polypeptide linkers. In cephalopods the circulating Hc is a decamer of these very large subunits. These enormous decamers may further aggregate to "dimers". So the molluscan Hc's molecules are truly enormous, the size of viruses - about 10 million Daltons!! with hundreds of binding sites. So the "dimers" you saw in the abstracts does not refer to dimers of polypeptides, but rather dimers of higher ordered structures (a terminology unique to Hc's). (Some invertebrate extracellular Hb's show hierarchal structures that resemble molluscan Hc's - interesting!) The allosteric unit of Hc's is the arthropod hexamer or molluscan 7-8 unit polypeptide, So very high nH values are possible and are, in fact seen (but rarely reported in abstracts!!). Also the allosteric mechanism generally requires more than the two states of the classic Jacob and Manot model.
Actually I was talking about the dimers I say in the strucutual maps of hemocyanins on pubmed: here is a example. I think saying "hemocyanin individual proteins are arrange in oligomer of varying arrangement..." in one sentence you could summarize 2 paragraphs. I don't know but I'm getting a serious urge to just start copying the stuff placed here and integrate it into the article, it boggles my mind that you can’t do it. It really is not hard to reorganize and rewrite a article. By the way I notices that some of the oxy and deoxy froms of hemocyanin also bind a soduim ion, whats that about? --BerserkerBen 20:33, 20 August 2005 (UTC)
[edit] Evolution of metalloprotein Oxygen carriers
A suggestion.
There will be a nice story linking Hb with haemocyanin, I expect, but don't know the details. Can anyone remark on it here or in a general article on them, or link appropriately? Midgley
- I don't think these two oxygen carriers are related, its likely as case of Parallel_evolution or Convergent_evolution, as multiple celled organism grow larger they needed as means to transport oxygen. --BerserkerBen 14:45, 29 January 2006 (UTC)
