myoglobin (mb) and hemoglobin (hb) have related, but different, roles in the body hemoglobin: found...
DESCRIPTION
Myoglobin is a single-subunit, α-helical protein, with a heme cofactor that binds O 2TRANSCRIPT
![Page 1: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/1.jpg)
Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body
Hemoglobin:• Found in red blood cells• Promotes diffusion of O2
throughout the body (binds O2 at lungs, releases at tissues)
Myoglobin:• Found in muscle cells• Promotes diffusion of O2
into and throughout muscle cell
![Page 2: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/2.jpg)
The oxygen-binding curves of Mb and Hb reflect their different functions
![Page 3: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/3.jpg)
Myoglobin is a single-subunit, α-helical protein, with a heme cofactor that binds O2
![Page 4: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/4.jpg)
A porphyrin ring forms the base structure of heme (with different hemes differing at X)
![Page 5: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/5.jpg)
The heme of myoglobin and hemoglobin is a protoporphyrin IX with a bound Fe2+
![Page 6: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/6.jpg)
In the globins, the heme iron binds O2 and the ‘proximal’ histidine of the protein
![Page 7: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/7.jpg)
Heme is held in place by the proximal His and by hydrophobic residues
distal
proximal
![Page 8: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/8.jpg)
Myoglobin is structurally similar to the subunits of hemoglobin
![Page 9: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/9.jpg)
Hemoglobin is a heterotetramer with two α- & two β-subunits (a dimer of αβ protomers)
α1β1
α2β2
![Page 10: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/10.jpg)
Hemoglobin can adopt two conformations, called ‘deoxyhemoglobin’ & ‘oxyhemoglobin’
α1
β1
β2
α2
α1
β1
β2
α2
deoxyhemoglobin oxyhemoglobin
![Page 11: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/11.jpg)
Hb’s conformations are also called ‘T-state’ (for tense) and ‘R-state’ (for relaxed)
(deoxyhemoglobin) (oxyhemoglobin)
![Page 12: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/12.jpg)
Oxygen binding promotes flattening of the porphyrin ring and shifting of helix F
![Page 13: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/13.jpg)
The proximal His links flattening of the heme to shifting of helix F in the T R transition
![Page 14: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/14.jpg)
Movement of helix F shifts the entire quaternary structure of hemoglobin
![Page 15: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/15.jpg)
The T and R states have shifted contacts between α & β subunits
T-state
R-state
![Page 16: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/16.jpg)
The T and R states have shifted contacts between α & β subunits
T-state R-state
![Page 17: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/17.jpg)
The T and R states have shifted contacts between α & β subunits
![Page 18: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/18.jpg)
![Page 19: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/19.jpg)
T-state salt bridges are broken in the R-state
![Page 20: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/20.jpg)
Heme also binds CO, NO, and H2S (with much higher affinity than O2)
P50 of CO binding to free heme is ~20,000x lower than P50 of O2 binding to free heme
![Page 21: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/21.jpg)
P50 of CO binding to globin-bound heme is ~200x lower than P50 of O2 binding to globin-bound heme
Globin structure reduces heme affinity for CO
![Page 22: Myoglobin (Mb) and Hemoglobin (Hb) have related, but different, roles in the body Hemoglobin: Found in red blood cells Promotes diffusion of O 2 throughout](https://reader036.vdocuments.us/reader036/viewer/2022062311/5a4d1b6c7f8b9ab0599b3b3b/html5/thumbnails/22.jpg)
CO is a competitive inhibitor and positive effector of O2 binding to hemoglobin