Myoglobin & Hemoglobin

Structure & Function of Biomolecules

Oxygen Transport Proteins

Myoglobin

Exhibits Michaelis-Menten properties

Hemoglobin

Exhibits allosteric properties

Myoglobin

Single polypeptide 16,700 daltons 8 a helices (A-H) Located in skeletal & cardiac muscle [high] in diving mammals like whale & seals

Heme prosthetic group

http://www.agen.ufl.edu/~chyn/age2062/lect/lect_02/3_27.gif

Heme Prosthetic Group

Heme (Fe2+) has affinity for O2.

N Fe N

Hematin (Fe3+) cannot bind O2.

Located in crevice where it is protected from oxidation.

N O

HO

Oxygen Binding to Myoglobin

O2 binds to only available coordination site on iron atom. His 93 (proximal his) binds directly to iron.

distal histidine

His 64 (distal his) stabilizes the O2 binding site.

proximal histidine
http://cwx.prenhall.com/horton/medialib/media_portfolio/text_images/FG04_44.JPG

O2 Binding Curve

Myoglobin has high affinity for O2.

100

saturation with O2

50

Allows myoglobin to act as O2 storage reserve. Releases O2 when pO2 becomes low indicating O2 deprivation.

2.8

tissues

P50 = 2.8 Torr

20

100

pO2 (partial pressure of O2) (Torr)

arterial pressure

Hemoglobin

Heterotetramer

HbA (most common)

a2b2

2 dimers

a1b1 and a2b2

Hemoglobin Structure

Each polypeptide chain resembles myoglobin tertiary structure but 1 sequence varies. Invariant residues indicate importance of those residues in function.

Oxygen Binding

(T state)

(R state)

O2 Binding to Hemoglobin

Hb exhibits + cooperativity.

QuickTime and a TIFF (Uncompressed) decompressor are neede d to see this picture.

http://cwx.prenhall.com/horton/medialib/media_portfolio/text_images/FG04_46.JPG

Hb Variants

HbA2

a2d2 Present in ~2% of adults

Embryonic Hb

a 2e 2 Has affinity for O2

Fetal Hb

a 2g 2 Has affinity for O2

http://oregonstate.edu/instruction/bb450/stryer/ch10/Slide27.jpg

Bohr Effect

CO2 pH

Some side groups remain protonated at lower pH. Stabilizes T state and promotes unloading of O2 to active tissues. Binding of CO2 also stabilizes T state.

CO2 binds to a amino groups.

http://cwx.prenhall.com/horton/medialib/media_portfolio/text_images/FG04_50.JPG

2, 3-Bisphosphoglycerate

Stabilizes deoxyHb (T state)

Facilitates unloading of O2 in tissue.
OO OO O P
-O

100

saturation with O2

- BPG

50

+ BPG

P O

O-

20

100

O-

pO2 (partial pressure of O2) (Torr)

2, 3-bisphosphoglycerate

2,3-BPG Binding to Hb

http://oregonstate.edu/instruction/bb450/stryer/ch10/Slide26.jpg

High Altitude and BPG

At higher altitudes, the [BPG] increases allowing Hb to unload O2 more easily.

http://www.bio.davidson.edu/Courses/anphys/1999/Yusi/dpgoxyhbgraph.jpg

Stored Blood & BPG

2,3-BPG becomes depleted in stored blood, so R state of Hb is stabilized. If BPG depleted blood is used for a transfusion, the R state Hb doesnt release O2. Add inosine to stored blood to maintain BPG levels.

CO Poisoining

CO is competitive inhibitor of O2.

Affinity is 200X greater than that of O2.

CO also inhibits unloading O2 of in tissues.