“Myoglobin”的意思、由来-开放百科全书

Myoglobin is the primary oxygen-carrying pigment of muscle tissues.^[3] High concentrations of myoglobin in muscle cells allow organisms to hold their breath for a longer period of time. Diving mammals such as whales and seals have muscles with particularly high abundance of myoglobin.^[2] Myoglobin is found in Type I muscle, Type II A and Type II B, but most texts consider myoglobin not to be found in smooth muscle.

Myoglobin was the first protein to have its three-dimensional structure revealed by X-ray crystallography.^[4] This achievement was reported in 1958 by John Kendrew and associates.^[5] For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.^[6] Despite being one of the most studied proteins in biology, its physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin can be viable and fertile but show many cellular and physiological adaptations to overcome the loss. Through observing these changes in myoglobin-deplete mice, it is hypothesised that myoglobin function relates to increased oxygen transport to muscle, oxygen storage and as a scavenger of reactive oxygen species.^[7]

Myoglobin can take the forms oxymyoglobin (MbO₂), carboxymyoglobin (MbCO), and metmyoglobin (met-Mb), analogously to hemoglobin taking the forms oxyhemoglobin (HbO₂), carboxyhemoglobin (HbCO), and methemoglobin (met-Hb).

Differences from hemoglobin

Like hemoglobin, myoglobin is a cytoplasmic protein that binds oxygen on a heme group. It harbors only one heme group, whereas hemoglobin has four. Although its heme group is identical to those in Hb, Mb has a higher affinity for oxygen than does hemoglobin. This difference is related to its different role: whereas hemoglobin transports oxygen, myoglobin's function is to store oxygen.

Meat color

Myoglobin contains hemes, pigments responsible for the colour of red meat. The colour that meat takes is partly determined by the degree of oxidation of the myoglobin. In fresh meat the iron atom is in the ferrous (+2) oxidation state bound to an oxygen molecule (O₂). Meat cooked well done is brown because the iron atom is now in the ferric (+3) oxidation state, having lost an electron. If meat has been exposed to nitrites, it will remain pink because the iron atom is bound to NO, nitric oxide (true of, e.g., corned beef or cured hams). Grilled meats can also take on a pink "smoke ring" that comes from the iron binding to a molecule of carbon monoxide.^[9] Raw meat packed in a carbon monoxide atmosphere also shows this same pink "smoke ring" due to the same principles. Notably, the surface of this raw meat also displays the pink color, which is usually associated in consumers' minds with fresh meat. This artificially induced pink color can persist, reportedly up to one year.^[10] Hormel and Cargill are both reported to use this meat-packing process, and meat treated this way has been in the consumer market since 2003.^[11]

Role in disease

Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute kidney injury.^[12] It is not the myoglobin itself that is toxic (it is a protoxin) but the ferrihemate portion that is dissociated from myoglobin in acidic environments (e.g., acidic urine, lysosomes).

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain.^[13] However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cardiac Troponin, ECG, and clinical signs should be taken into account to make the diagnosis.

Structure and bonding

Myoglobin belongs to the globin superfamily of proteins, and as with other globins, consists of eight alpha helices connected by loops. Myoglobin contains 154 amino acids.^[15]

Myoglobin contains a porphyrin ring with an iron at its center. A proximal histidine group (His-93) is attached directly to iron, and a distal histidine group (His-64) hovers near the opposite face.^[15] The distal imidazole is not bonded to the iron but is available to interact with the substrate O₂. This interaction encourages the binding of O₂, but not carbon monoxide (CO), which still binds about 240× more strongly than O₂.

The binding of O₂ causes substantial structural change at the Fe center, which shrinks in radius and moves into the center of N4 pocket. O₂-binding induces "spin-pairing": the five-coordinate ferrous deoxy form is high spin and the six coordinate oxy form is low spin and diamagnetic.{{Citation needed|reason=Reliable source needed for the whole sentence|date=March 2017}}

Synthetic analogues

Many models of myoglobin have been synthesized as part of a broad interest in transition metal dioxygen complexes. A well known example is the picket fence porphyrin, which consists of a ferrous complex of a sterically bulky derivative of tetraphenylporphyrin.^[16] In the presence of an imidazole ligand, this ferrous complex reversibly binds O₂. The O₂ substrate adopts a bent geometry, occupying the sixth position of the iron center. A key property of this model is the slow formation of the μ-oxo dimer, which is an inactive diferric state. In nature, such deactivation pathways are suppressed by protein matrix that prevents close approach of the Fe-porphyrin assemblies.^[17]

See also

References

1. ^{{cite journal | vauthors = Hardison RC | title = Evolution of Hemoglobin and Its Genes | journal = Cold Spring Harb Perspect Med | volume = 2 | issue = 12 | pages = a011627 | date = Dec 2012 | pmid = 23209182 | doi = 10.1101/cshperspect.a011627 }}
2. ^¹{{cite book | author = Nelson DL, Cox MM | title = Lehninger Principles of Biochemistry | publisher = Worth Publishers | location = New York | year = 2000 | page = 206 | edition = 3rd | isbn = 0-7167-6203-X | url=https://books.google.com/books?id=5Ek9J4p3NfkC&dq=nelson+2000+Lehninger+Principles+of+Biochemistry&q=myoglobin}} (Google books link is the 2008 edition)
3. ^{{cite journal | vauthors = Ordway GA, Garry DJ | title = Myoglobin: an essential hemoprotein in striated muscle | journal = The Journal of Experimental Biology | volume = 207 | issue = Pt 20 | pages = 3441–6 | date = Sep 2004 | pmid = 15339940 | doi = 10.1242/jeb.01172 }}
4. ^[https://www.nsf.gov/news/news_summ.jsp?cntn_id=100689 (U.S.) National Science Foundation: Protein Data Bank Chronology (Jan. 21, 2004)]. Retrieved 3.17.2010
5. ^{{cite journal | vauthors = Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, Phillips DC | title = A three-dimensional model of the myoglobin molecule obtained by x-ray analysis | journal = Nature | volume = 181 | issue = 4610 | pages = 662–6 | date = Mar 1958 | pmid = 13517261 | doi = 10.1038/181662a0 | bibcode = 1958Natur.181..662K }}
6. ^The Nobel Prize in Chemistry 1962
7. ^{{cite journal | vauthors = Garry DJ, Kanatous SB, Mammen PP | title = Molecular insights into the functional role of myoglobin | journal = Advances in Experimental Medicine and Biology | volume = 618 | pages = 181-93 | date = 2007 | pmid = 18269197 | doi = 10.1007/978-0-387-75434-5_14 }}
8. ^{{cite journal | vauthors = Akaboshi E | title = Cloning of the human myoglobin gene | journal = Gene | volume = 33 | issue = 3 | pages = 241–9 | year = 1985 | pmid = 2989088 | doi = 10.1016/0378-1119(85)90231-8 }}
9. ^{{cite book | author = McGee H | title = On Food and Cooking: The Science and Lore of the Kitchen |publisher=Scribner |location=New York |year=2004 |isbn=0-684-80001-2 |page=148 }}
10. ^{{cite journal | vauthors = Fraqueza MJ, Barreto AS | title = Gas mixtures approach to improve turkey meat shelf life under modified atmosphere packaging: the effect of carbon monoxide | journal = Poultry Science | volume = 90 | issue = 9 | pages = 2076–84 | date = Sep 2011 | pmid = 21844276 | doi = 10.3382/ps.2011-01366 }}
11. ^{{cite web | url = http://www.startribune.com/business/11223451.html | title = Meat companies defend use of carbon monoxide | author = Associated Press | date = 2007-10-30 | work = Business | publisher = Minneapolis Star Tribune }}
12. ^{{cite journal | vauthors = Naka T, Jones D, Baldwin I, Fealy N, Bates S, Goehl H, Morgera S, Neumayer HH, Bellomo R | title = Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report | journal = Critical Care | volume = 9 | issue = 2 | pages = R90-5 | date = Apr 2005 | pmid = 15774055 | pmc = 1175920 | doi = 10.1186/cc3034 }}
13. ^{{cite journal | vauthors = Weber M, Rau M, Madlener K, Elsaesser A, Bankovic D, Mitrovic V, Hamm C | title = Diagnostic utility of new immunoassays for the cardiac markers cTnI, myoglobin and CK-MB mass | journal = Clinical Biochemistry | volume = 38 | issue = 11 | pages = 1027–30 | date = Nov 2005 | pmid = 16125162 | doi = 10.1016/j.clinbiochem.2005.07.011 }}
14. ^{{cite journal | vauthors = Drago RS | title = Free radical reactions of transition metal systems | journal = Coordination Chemistry Reviews | year = 1980 | volume = 32 | pages = 97–110 | doi = 10.1016/S0010-8545(00)80372-0 | issue = 2 }}
15. ^¹{{UniProt Full|P02144}}
16. ^{{cite journal | vauthors = Collman JP, Brauman JI, Halbert TR, Suslick KS | title = Nature of O2 and CO binding to metalloporphyrins and heme proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 10 | pages = 3333–7 | date = Oct 1976 | pmid = 1068445 | pmc = 431107 | doi = 10.1073/pnas.73.10.3333 | bibcode = 1976PNAS...73.3333C }}
17. ^{{cite book | author = Lippard SJ, Berg JM | title = Principles of Bioinorganic Chemistry | publisher = University Science Books | location = Mill Valley, CA | year = 1994 | isbn = 0-935702-73-3 }}