Editing Hemocyanin

{{Short description|Proteins that transport oxygen throughout the bodies of some invertebrate animals}}
{{Infobox protein family 
| Symbol = Hemocyanin_M 
| Name = Hemocyanin, copper containing domain 
| image = Hemocyanin2.jpg
| width = 
| caption = Single oxygenated functional unit from the hemocyanin of an [[octopus]]
| Pfam= PF00372
| InterPro= IPR000896
| SMART= 
| Prosite = PDOC00184
| SCOP = 1lla
| TCDB = 
| OPM family= 
| OPM protein= 
| PDB= 
{{PDB3|1oxy}} :110-373   {{PDB3|1nol}} :110-373   {{PDB3|1lla}} :110-373   
{{PDB3|1ll1}} :110-373   {{PDB3|1hc1}}A:136-393   {{PDB3|1hcy}}D:136-393   
{{PDB3|1hc6}}B:136-393   {{PDB3|1hc4}}C:136-393   {{PDB3|1hc3}}C:136-393   
{{PDB3|1hc5}}C:136-393   {{PDB3|1hc2}}C:136-393   
}} 
{{Infobox protein family
| Symbol = Hemocyanin_N
| Name = Hemocyanin, all-alpha domain
| image = PDB 1hcy EBI.jpg
| width = 
| caption = Crystal structure of hexameric haemocyanin from ''[[Panulirus interruptus]]'' refined at 3.2 angstroms resolution
| Pfam = PF03722
| Pfam_clan =  
| InterPro = IPR005204
| SMART = 
| PROSITE = PDOC00184
| MEROPS = 
| SCOP = 1lla
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{Infobox protein family
| Symbol = Hemocyanin_C
| Name = Hemocyanin, ig-like domain
| image = PDB 1oxy EBI.jpg
| width = 
| caption = crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences
| Pfam = PF03723
| Pfam_clan =  
| InterPro = IPR005203
| SMART = 
| PROSITE = PDOC00184
| MEROPS = 
| SCOP = 1lla
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
'''Hemocyanins''' (also spelled '''haemocyanins''' and abbreviated '''Hc''') are  [[protein]]s that transport oxygen throughout the bodies of some [[invertebrate]] animals. These [[metalloprotein]]s contain two [[copper]] atoms that reversibly bind a single [[oxygen]] molecule (O<sub>2</sub>). They are second only to [[hemoglobin]] in frequency of use as an oxygen transport molecule. Unlike the hemoglobin in [[red blood cells]] found in [[vertebrates]], hemocyanins are not confined in blood cells, but are instead suspended directly in the [[hemolymph]]. Oxygenation causes a [[color]] change between the colorless Cu(I) deoxygenated form and the [[blue]] Cu(II) oxygenated form.<ref name="pmid24486681">{{cite journal | vauthors = Coates CJ, Nairn J | title = Diverse immune functions of hemocyanins | journal = Developmental and Comparative Immunology | volume = 45 | issue = 1 | pages = 43–55 | date = July 2014 | pmid = 24486681 | doi = 10.1016/j.dci.2014.01.021 }}</ref>

== Species distribution ==
Hemocyanin was first discovered in ''[[Octopus vulgaris]]'' by [[Leon Fredericq]] in 1878. The presence of copper in molluscs was detected even earlier by [[Bartolomeo Bizio]] in 1833.<ref>{{Cite journal | vauthors = Ghiretti-Magaldi A, Ghiretti F |date=1992 |title=The pre-history of hemocyanin. The discovery of copper in the blood of molluscs |url=http://link.springer.com/10.1007/BF01919143 |journal=Experientia |language=en |volume=48 |issue=10 |pages=971–972 |doi=10.1007/BF01919143 |s2cid=33290596 |issn=0014-4754}}</ref> Hemocyanins are found in the [[Mollusca]] and [[Arthropoda]], including [[cephalopod]]s and [[crustacean]]s, and utilized by some land arthropods such as the tarantula ''[[Eurypelma californicum]]'',<ref name="Voit_2000">{{cite journal | vauthors = Voit R, Feldmaier-Fuchs G, Schweikardt T, Decker H, Burmester T | title = Complete sequence of the 24-mer hemocyanin of the tarantula Eurypelma californicum. Structure and intramolecular evolution of the subunits | journal = The Journal of Biological Chemistry | volume = 275 | issue = 50 | pages = 39339–39344 | date = December 2000 | pmid = 10961996 | doi = 10.1074/jbc.M005442200 | doi-access = free }}</ref> the [[emperor scorpion]],<ref name="pmid22403673">{{cite journal | vauthors = Jaenicke E, Pairet B, Hartmann H, Decker H | title = Crystallization and preliminary analysis of crystals of the 24-meric hemocyanin of the emperor scorpion (Pandinus imperator) | journal = PLOS ONE | volume = 7 | issue = 3 | pages = e32548 | year = 2012 | pmid = 22403673 | pmc = 3293826 | doi = 10.1371/journal.pone.0032548 | doi-access = free | bibcode = 2012PLoSO...732548J }}
* {{cite web |date=June 22, 2012 |title=The blue blood of the emperor scorpion x-rayed |website=Johannes Gutenberg-Universität Mainz |url=http://www.uni-mainz.de/presse/15460_ENG_HTML.php |access-date=March 18, 2013 |archive-date=May 6, 2022 |archive-url=https://web.archive.org/web/20220506035019/https://www.uni-mainz.de/presse/15460_ENG_HTML.php |url-status=dead }}</ref> and the centipede ''[[Scutigera coleoptrata]]''.  Also, larval storage proteins in many insects appear to be derived from hemocyanins.<ref name="molbeva040129">{{cite journal | vauthors = Beintema JJ, Stam WT, Hazes B, Smidt MP | title = Evolution of arthropod hemocyanins and insect storage proteins (hexamerins) | journal = Molecular Biology and Evolution | volume = 11 | issue = 3 | pages = 493–503 | date = May 1994 | pmid = 8015442 | doi = 10.1093/oxfordjournals.molbev.a040129 | doi-access = free }}</ref>

== The hemocyanin superfamily ==
The arthropod hemocyanin [[superfamily (proteins)|superfamily]] is composed of [[phenoloxidase]]s, [[hexamerin]]s, [[pseudohemocyanin]]s or [[cryptocyanin]]s, and ([[diptera]]n) hexamerin receptors.<ref>{{cite journal | vauthors = Burmester T | title = Origin and evolution of arthropod hemocyanins and related proteins | journal = Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology | volume = 172 | issue = 2 | pages = 95–107 | date = February 2002 | pmid = 11916114 | doi = 10.1007/s00360-001-0247-7 | s2cid = 26023927 }}</ref>

Phenoloxidase are copper-containing tyrosinases. These proteins are involved in the process of sclerotization of arthropod cuticle, in wound healing, and humoral immune defense. Phenoloxidase is synthesized by [[Zymogen|zymogens]] and are activated by cleaving an [[N-terminus|N-terminal]] [[peptide]].<ref>{{cite journal | vauthors = Cerenius L, Söderhäll K | title = The prophenoloxidase-activating system in invertebrates | journal = Immunological Reviews | volume = 198 | issue = 1 | pages = 116–126 | date = April 2004 | pmid = 15199959 | doi = 10.1111/j.0105-2896.2004.00116.x | s2cid = 10614298 }}</ref>

Hexamerins are storage proteins commonly found in insects. These proteins are synthesized by the larval [[fat body]] and are associated with molting cycles or nutritional conditions.<ref>{{Cite journal|vauthors=Terwilliger NB|date=1999|title=Hemolymph Proteins and Molting in Crustaceans and Insects|journal=American Zoologist|volume=39|issue=3|pages=589–599|doi=10.1093/icb/39.3.589|doi-access=free}}</ref>

Pseudohemocyanin and cryptocyanins genetic sequences are closely related to hemocyanins in crustaceans. These proteins have a similar structure and function, but lack the [[copper]] binding sites.<ref>{{cite journal | vauthors = Terwilliger NB, Dangott L, Ryan M | title = Cryptocyanin, a crustacean molting protein: evolutionary link with arthropod hemocyanins and insect hexamerins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 5 | pages = 2013–2018 | date = March 1999 | pmid = 10051586 | pmc = 26728 | doi = 10.1073/pnas.96.5.2013 | doi-access = free | bibcode = 1999PNAS...96.2013T }}</ref>

The evolutionary changes within the phylogeny of the hemocyanin superfamily are closely related to the emergence of these different proteins in various species. The proteins within this superfamily would not be well understood without the extensive studies of hemocyanin in arthropods.<ref name= Burmester>{{cite journal | vauthors = Burmester T | title = Molecular evolution of the arthropod hemocyanin superfamily | journal = Molecular Biology and Evolution | volume = 18 | issue = 2 | pages = 184–195 | date = February 2001 | pmid = 11158377 | doi = 10.1093/oxfordjournals.molbev.a003792 | doi-access = free }}</ref>

== Structure and mechanism ==

Although the respiratory function of hemocyanin is similar to that of hemoglobin, there are a significant number of differences in its molecular structure and mechanism. Whereas hemoglobin carries its [[iron]] atoms in [[porphyrin]] rings ([[heme]] groups), the [[copper]] atoms of hemocyanin are bound as [[prosthetic group]]s coordinated by [[histidine]] residues. Each hemocyanin monomer holds a pair of copper(I) cations in place via interactions with the [[imidazole]] rings of six histidine residues.<ref name="Rannulu, N. S.">{{cite journal | vauthors = Rannulu NS, Rodgers MT | title = Solvation of copper ions by imidazole: structures and sequential binding energies of Cu+(imidazole)x, x = 1-4. Competition between ion solvation and hydrogen bonding | journal = Physical Chemistry Chemical Physics | volume = 7 | issue = 5 | pages = 1014–1025 | date = March 2005 | pmid = 19791394 | doi = 10.1039/b418141g | bibcode = 2005PCCP....7.1014R }}</ref> It has been noted that species using hemocyanin for oxygen transportation include [[crustaceans]] living in cold environments with low oxygen pressure. Under these circumstances hemoglobin oxygen transportation is less efficient than hemocyanin oxygen transportation.<ref name="pmid22791630">{{cite journal | vauthors = Strobel A, Hu MY, Gutowska MA, Lieb B, Lucassen M, Melzner F, Pörtner HO, Mark FC | display-authors = 6 | title = Influence of temperature, hypercapnia, and development on the relative expression of different hemocyanin isoforms in the common cuttlefish Sepia officinalis | journal = Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology | volume = 317 | issue = 8 | pages = 511–523 | date = December 2012 | pmid = 22791630 | doi = 10.1002/jez.1743 | url = https://epic.awi.de/id/eprint/31021/2/Strobel_etal_2012a.pdf }}</ref> Nevertheless, there are also terrestrial arthropods using hemocyanin, notably spiders and scorpions, that live in warm climates. The molecule is conformationally stable and fully functioning at temperatures up to 90 degrees C.<ref>{{cite journal | vauthors = Sterner R, Vogl T, Hinz HJ, Penz F, Hoff R, Föll R, Decker H | title = Extreme thermostability of tarantula hemocyanin | journal = FEBS Letters | volume = 364 | issue = 1 | pages = 9–12 | date = May 1995 | pmid = 7750550 | doi = 10.1016/0014-5793(95)00341-6 | doi-access =  }}</ref>

Most hemocyanins bind with oxygen non-[[Cooperative binding|cooperatively]] and are roughly one-fourth as efficient as hemoglobin at transporting oxygen per amount of blood. Hemoglobin binds oxygen cooperatively due to steric [[protein folding|conformation]] changes in the [[protein complex]], which increases hemoglobin's affinity for oxygen when partially oxygenated. In some hemocyanins of [[horseshoe crab]]s and some other species of [[arthropods]], cooperative binding is observed, with [[Hill coefficient]]s of 1.6–3.0.  Hill coefficients vary depending on species and laboratory measurement settings. Hemoglobin, for comparison, has a Hill coefficient of usually 2.8–3.0. In these cases of [[cooperative binding]] hemocyanin was arranged in protein sub-complexes of 6 subunits (hexamer) each with one oxygen binding site; binding of oxygen on one unit in the complex would increase the affinity of the neighboring units. Each hexamer complex was arranged together to form a larger complex of dozens of hexamers. In one study, cooperative binding was found to be dependent on hexamers being arranged together in the larger complex, suggesting cooperative binding between hexamers. Hemocyanin oxygen-binding profile is also affected by dissolved salt ion levels and [[pH]].<ref name="pmid9187351">{{cite journal | vauthors = Perton FG, Beintema JJ, Decker H | title = Influence of antibody binding on oxygen binding behavior of Panulirus interruptus hemocyanin | journal = FEBS Letters | volume = 408 | issue = 2 | pages = 124–126 | date = May 1997 | pmid = 9187351 | doi = 10.1016/S0014-5793(97)00269-X | doi-access =  }}</ref>

Hemocyanin is made of many individual subunit proteins, each of which contains two [[copper]] atoms and can bind one oxygen molecule (O<sub>2</sub>). Each subunit weighs about 75 [[Dalton (unit)|kilodaltons]] (kDa). Subunits may be arranged in [[protein dimer|dimer]]s or [[hexamer]]s depending on species; the dimer or hexamer complex is likewise arranged in chains or clusters with weights exceeding 1500 kDa. The subunits are usually [[wiktionary:Homogeneous|homogeneous]], or [[heterogeneous]] with two variant subunit types. Because of the large size of hemocyanin, it is usually found free-floating in the blood, unlike hemoglobin.<ref name="pmid1126935">{{cite journal | vauthors = Waxman L | title = The structure of arthropod and mollusc hemocyanins | journal = The Journal of Biological Chemistry | volume = 250 | issue = 10 | pages = 3796–3806 | date = May 1975 | pmid = 1126935 | doi = 10.1016/S0021-9258(19)41469-5 | doi-access = free }}</ref>

[[File:Molluscan hemocyanin (4YD9).png|thumb|center|upright=3|The 3.8 MDa structure of molluscan [[Japanese flying squid]] hemocyanin. It is a homodecamer of five dimers arranged into a 31 nm diameter cylinder. Each monomer has a string of eight individual subunits each with a Cu<sub>2</sub>O<sub>2</sub> binding site.<ref>{{Cite journal |last1=Gai |first1=Zuoqi |last2=Matsuno |first2=Asuka |last3=Kato |first3=Koji |last4=Kato |first4=Sanae |last5=Khan |first5=Md Rafiqul Islam |last6=Shimizu |first6=Takeshi |last7=Yoshioka |first7=Takeya |last8=Kato |first8=Yuki |last9=Kishimura |first9=Hideki |last10=Kanno |first10=Gaku |last11=Miyabe |first11=Yoshikatsu |last12=Terada |first12=Tohru |last13=Tanaka |first13=Yoshikazu |last14=Yao |first14=Min |date=2015 |title=Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution |journal=Structure |language=en |volume=23 |issue=12 |pages=2204–2212 |doi=10.1016/j.str.2015.09.008|doi-access=free |pmid=26602184 }}</ref> {{PDB|4YD9}}]]

Hexamers are characteristic of arthropod hemocyanins.<ref name="pmid8561049">{{cite book|title=Advances in Protein Chemistry |vauthors=van Holde KE, Miller KI|publisher=Academic Press |year=1995 |isbn=978-0-12-034247-1| veditors = Anfinsen CB, Richards FM, Edsall JT, Eisenberg DS |volume=47 |pages=1–81 |chapter=Hemocyanins |doi=10.1016/S0065-3233(08)60545-8|pmid=8561049 }}</ref> A hemocyanin of the tarantula ''Eurypelma californicum''<ref name="Voit_2000"/> is made up of 4 hexamers or 24 peptide chains. A hemocyanin from the house centipede ''Scutigera coleoptrata''<ref name="pmid12823556">{{cite journal | vauthors = Kusche K, Hembach A, Hagner-Holler S, Gebauer W, Burmester T | title = Complete subunit sequences, structure and evolution of the 6 x 6-mer hemocyanin from the common house centipede, Scutigera coleoptrata | journal = European Journal of Biochemistry | volume = 270 | issue = 13 | pages = 2860–2868 | date = July 2003 | pmid = 12823556 | doi = 10.1046/j.1432-1033.2003.03664.x | doi-access = free }}</ref> is made up of 6 hexamers or 36 chains. [[Horseshoe crabs]] have an 8-hexamer (i. e. 48-chain) hemocyanin. Simple hexamers are found in the spiny lobster ''Panulirus interruptus'' and the isopod ''Bathynomus giganteus''.<ref name=pmid8561049/> Peptide chains in [[crustaceans]] are about 660 amino acid residues long, and in [[chelicerates]] they are about 625. In the large complexes there is a variety of variant chains, all about the same length; pure components do not usually self-assemble.{{citation needed|date=February 2017}}

== Catalytic activity ==

[[Image:deoxyhemocyanin_full.png|thumb|class=skin-invert-image|right|A hemocyanin active site in the absence of O<sub>2</sub> (each Cu center is a cation, charges not shown).]]
[[Image:oxyhemocyanin_full.png|thumb|class=skin-invert-image|right|O<sub>2</sub>-bound form of a hemocyanin active site (the Cu<sub>2</sub> center is a dication, charge not shown).]]
Hemocyanin is homologous to the phenol oxidases (e.g. [[tyrosinase]]) since both proteins have [[histidine]] residues, called "type 3" copper-binding coordination centers, as do the enzymes [[tyrosinase]] and [[catechol oxidase]].<ref name="pmid10916160">{{cite journal | vauthors = Decker H, Tuczek F | title = Tyrosinase/catecholoxidase activity of hemocyanins: structural basis and molecular mechanism | journal = Trends in Biochemical Sciences | volume = 25 | issue = 8 | pages = 392–397 | date = August 2000 | pmid = 10916160 | doi = 10.1016/S0968-0004(00)01602-9 }}</ref> In both cases inactive precursors to the enzymes (also called [[zymogen]]s or proenzymes) must be activated first. This is done by removing the amino acid that blocks the entrance channel to the active site when the proenzyme is not active. There is currently no other known modifications necessary to activate the proenzyme and enable catalytic activity. [[Conformational_isomerism|Conformational]] differences determine the type of catalytic activity that the hemocyanin is able to perform.<ref name=Decker_2007>{{cite journal | vauthors = Decker H, Schweikardt T, Nillius D, Salzbrunn U, Jaenicke E, Tuczek F | title = Similar enzyme activation and catalysis in hemocyanins and tyrosinases | journal = Gene | volume = 398 | issue = 1–2 | pages = 183–191 | date = August 2007 | pmid = 17566671 | doi = 10.1016/j.gene.2007.02.051 }}</ref> Hemocyanin also exhibits [[phenol oxidase]] activity, but with slowed kinetics from greater steric bulk at the active site.  Partial denaturation actually improves hemocyanin's phenol oxidase activity by providing greater access to the active site.<ref name="pmid24486681" /><ref name="pmid10916160"/>

== Spectral properties ==

[[File:Hemocyanin Example.jpg|thumb|The underside of the '''carapace''' of a red rock crab (''[[Cancer productus]]''). The purple coloring is caused by hemocyanin.]]
Spectroscopy of oxyhemocyanin shows several salient features:<ref name=Tolman/>
# Resonance [[Raman spectroscopy]] shows that {{chem|O|2}} is bound in a symmetric environment (ν(O-O) is not IR-allowed).
# OxyHc is [[electron paramagnetic resonance|EPR]]-silent indicating the absence of unpaired electrons
# [[Infrared spectroscopy]] shows ν(O-O) of 755&nbsp;cm<sup>−1</sup>

Much work has been devoted to preparing synthetic analogues of the active site of hemocyanin.<ref name="Tolman">{{cite journal | vauthors = Elwell CE, Gagnon NL, Neisen BD, Dhar D, Spaeth AD, Yee GM, Tolman WB | title = Copper-Oxygen Complexes Revisited: Structures, Spectroscopy, and Reactivity | journal = Chemical Reviews | volume = 117 | issue = 3 | pages = 2059–2107 | date = February 2017 | pmid = 28103018 | pmc = 5963733 | doi = 10.1021/acs.chemrev.6b00636 }}</ref> One such model, which features a pair of copper centers bridged side-on by peroxo ligand, shows ν(O-O) at 741&nbsp;cm<sup>−1</sup> and a UV-Vis spectrum with absorbances at 349 and 551&nbsp;nm.  Both of these measurements agree with the experimental observations for oxyHc.<ref name="Kitajima">{{cite journal|display-authors=6|vauthors=Kitajima N, Fujisawa K, Fujimoto C, Morooka Y, Hashimoto S, Kitagawa T, Toriumi K, Tatsumi K, Nakamura A|date=1992|title=A new model for dioxygen binding in hemocyanin. Synthesis, characterization, and molecular structure of the μ-η2:η2 peroxo dinuclear copper(II) complexes, [Cu(BH(3,5-R2pz)3)]2(O2) (R = i-Pr and Ph)|journal=Journal of the American Chemical Society|volume=114|issue=4|pages=1277–91|doi=10.1021/ja00030a025}}</ref> The Cu-Cu separation in the model complex is 3.56 Å, that of oxyhemocyanin is ca. 3.6 Å (deoxyHc: ca. 4.6 Å).<ref name=Kitajima/><ref>{{cite journal | vauthors = Gaykema WP, Hol WG, Vereijken JM, Soeter NM, Bak HJ, Beintema JJ |title=3.2 Å structure of the copper-containing, oxygen-carrying protein Panulirus interruptus haemocyanin |journal=Nature |volume=309 |issue=5963 |pages=23–9 |year=1984 |doi=10.1038/309023a0 |bibcode=1984Natur.309...23G |s2cid=4260701 }}</ref><ref>{{cite journal|display-authors=6|vauthors=Kodera M, Katayama K, Tachi Y, Kano K, Hirota S, Fujinami S, Suzuki M|date=1999|title=Crystal Structure and Reversible O2-Binding of a Room Temperature Stable μ-η2:η2-Peroxodicopper(II) Complex of a Sterically Hindered Hexapyridine Dinucleating Ligand|journal=Journal of the American Chemical Society|volume=121|issue=47|pages=11006–7|doi=10.1021/ja992295q}}</ref>

== Anticancer effects ==

The hemocyanin found in the blood of the Chilean abalone, ''[[Concholepas concholepas]]'', has immunotherapeutic effects against [[bladder cancer]] in murine models. Mice primed with ''C. concholepas'' before implantation of bladder [[tumor]] (MBT-2) cells. Mice treated with ''C. concholepas'' hemocyanin showed antitumor effects: prolonged survival, decreased tumor growth and incidence, and lack of toxic effects and may have a potential use in future immunotherapy for superficial bladder cancer.<ref name=Atala_2006>{{cite journal |doi=10.1016/j.juro.2006.09.002 |title=This Month in Investigative Urology |journal=The Journal of Urology |volume=176 |issue=6 |pages=2335–6 |year=2006 | vauthors = Atala A }}</ref><!--primary source-->

[[Keyhole limpet hemocyanin]] (KLH) is an immune stimulant derived from circulating glycoproteins of the marine mollusk ''Megathura crenulata''. KLH has been shown to be a significant treatment against the proliferations of breast cancer, pancreas cancer, and prostate cancer cells when delivered in vitro. Keyhole limpet hemocyanin inhibits growth of human Barrett's esophageal cancer through both apoptic and nonapoptic mechanisms of cell death.<ref name=McFadden_2003>{{cite journal | vauthors = McFadden DW, Riggs DR, Jackson BJ, Vona-Davis L | title = Keyhole limpet hemocyanin, a novel immune stimulant with promising anticancer activity in Barrett's esophageal adenocarcinoma | journal = American Journal of Surgery | volume = 186 | issue = 5 | pages = 552–555 | date = November 2003 | pmid = 14599624 | doi = 10.1016/j.amjsurg.2003.08.002 }}</ref><!--primary source-->

== Case studies: environmental impact on hemocyanin levels ==
A 2003 study of the effect of culture conditions of blood metabolites and hemocyanin of the white shrimp ''[[Litopenaeus vannamei]]'' found that the levels of hemocyanin, oxyhemocyanin in particular, are affected by the diet. The study compared oxyhemocyanin levels in the blood of white shrimp housed in an indoor pond with a commercial diet with that of white shrimp housed in an outdoor pond with a more readily available protein source (natural live food) as well. Oxyhemocyanin and blood glucose levels were higher in shrimp housed in outdoor ponds. It was also found that blood metabolite levels tended to be lower in low activity level species, such as crabs, lobsters, and the indoor shrimp when compared to the outdoor shrimp. This correlation is possibly indicative of the morphological and physiological evolution of crustaceans. The levels of these blood proteins and metabolites appear to be dependent on energetic demands and availability of those energy sources.<ref name=Pascual_2006>{{cite journal | vauthors = Pascual C, Gaxiola G, Rosas C |title=Blood metabolites and hemocyanin of the white shrimp, Litopenaeus vannamei: The effect of culture conditions and a comparison with other crustacean species |journal=Marine Biology |volume=142 |issue=4 |pages=735–745 |year=2003 |doi=10.1007/s00227-002-0995-2 |s2cid=82961592 }}</ref>

== See also ==
* [[Atlantic horseshoe crab#Blood|Atlantic horseshoe crab blood]]
* [[Keyhole limpet hemocyanin]]
* [[Hemoglobin]]
* [[Myoglobin]]
* [[Respiratory pigment]]
{{Clear}}

== References ==
{{reflist|30em}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Rehm P, Pick C, Borner J, Markl J, Burmester T | title = The diversity and evolution of chelicerate hemocyanins | journal = BMC Evolutionary Biology | volume = 12 | pages = 19 | date = February 2012 | pmid = 22333134 | pmc = 3306762 | doi = 10.1186/1471-2148-12-19 | doi-access = free }}
* {{cite book |vauthors=Ali SA, Abbasi A | title = Scorpion Hemocyanin: The blue blood | year = 2011 | publisher = VDM Verlag Dr. Müller | location= Saarbrücken | isbn =  978-3-639-33725-9 | page = 160 }}
{{refend}}

== External links ==
{{commons category|Hemocyanin}}
*[http://www.pdbe.org/emsearch/hemocyanin* 3D hemocyanin structures in the EM Data Bank (EMDB)]
*{{PDBe-KB2|P04253|Hemocyanin II}}

{{Hemeproteins}}

{{Authority control}}

[[Category:Metalloproteins]]
[[Category:Blood proteins]]
[[Category:Copper proteins]]
[[Category:Immunostimulants]]
[[Category:Respiratory pigments]]