Hemoglobin, an Allosteric Protein

which inhibitor

competitive

which inhibitor

uncompetitive

which inhibitor

noncompetitive

which inhibitor

competitive

which inhibitor

uncompetitive

which inhibitor

noncompetitive

which inhibitor

competitive

which inhibitor

uncompetitive

which inhibitor

noncompetitive

As aerobic organisms, all our cells require what to burn fuel (carbohydrates, fats, etc.) to generate energy to do work (just like a gasoline engine in a car)

oxygen

O2 is what soluble in aqueous solutions

poorly

erythrocytes (red blood cells) are specialized for transporting what

oxygen

hemoglobin

the oxygen-binding protein in red blood cell

hemoglobin

RBCs use what to bind oxygen in the lungs, and release it at
tissues that need it

is hemoglobin an enzyme

no

tetramer

hemoglobin is a what consisting of two α subunits (141 residues)
and two β subunits (146 residues) (two different proteins and genes)

both of hemoglobin’s subunits have a bound heme prosthetic group containing an Fe2+ what atom

iron

protoporphyrin

heme consists of a complex organic ring structure, what, with a bound Fe2+ atom

the hemoglobin tetramer is a pair of αβ dimers (which structure)

quaternary

In what, which corresponds to the T state of this allosteric protein, the αβ dimers are linked by an extensive interface

deoxyhemoglobin

allosteric protein

binding of a ligand or molecule to one site affects the binding properties of another site on the same protein

modulator/regulator

ligand that binds to an allosteric protein to induce a conformational change

modulator is a normal ligand

homotropic

modulator is not the normal ligand

heterotropic

ligand

In a multisubunit protein, a conformational change in one subunit
affects the conformation of other subunits to alter their what binding

more stable when O2 is absent

T state

higher affinity for O2 (O2 bound)

R state

deoxyhemoglobin

T state

oxyhemoglobin

R state

When one hemoglobin subunit binds oxygen, the other three subunits
shift to the which state, which allows oxygen to bind more easily
– an allosteric conformational change

R

cooperativity

Hemoglobin is an allosteric protein that displays what in oxygen binding and release

globin

hemoglobin is a member of the what protein family

globins

protein family found in animals, plants and some bacteria

globins
– highly conserved what structure: eight α-helices connected by bends

tertiary

O2

globins = protein family found in animals, plants and some bacteria
– most function in what transport or storage

muscle

Myoglobin (153 residues) is an oxygen binding protein in cardiac and skeletal what cells

heme

Like hemoglobin, myoglobin has a bound what prosthetic group, which binds oxygen. The iron in the myoglobin heme gives cooked meat its red color

monomeric

Unlike hemoglobin, myoglobin is a what protein

Hemoglobin subunits and Myoglobin are Structurally what

Similar

The binding of oxygen by hemoglobin is what

cooperative

The binding of oxygen by myoglobin is what

uncooperative

pressure

Oxygen binding is related to the partial what of oxygen (pO2)

oxygen

Partial pressure is the fraction of the mixture of gases that is due to one gas - in
this case, what. At sea level, 1 atmosphere of pressure = 760 torr. Air is 21%
oxygen, so the partial pressure of oxygen is 159 torr (kind of like gas concentration)

In where, where hemoglobin binds oxygen, the partial pressure of oxygen is
~100 tor

lungs

In where, where hemoglobin needs to deliver oxygen, the partial pressure of oxygen is ~ 20 torr – there is much less oxygen near the cells that require it for their metabolic need

tissues

curves

Hemoglobin and myoglobin have oxygen-binding what with different shapes

Michaelis-Menten

Myoglobin binding to oxygen follows a ‘what’ curve

allostery

Hemoglobin’s binding curve does not follow a ‘Michaelis-Menten, it indicates what at work

Although hemoglobin doesn’t bind oxygen as ‘well’ as myoglobin, it can release oxygen much what at the sites where it is needed

better

?% O2 released by hemoglobin versus ?% of O2 released by myoglobin

66, 7

The iron lies in the middle of the protoporphyrin bound to how many nitrogens

four

coordination

Besides the four nitrogen, Iron can form two additional bonds, called the fifth and sixth what sites

Which coordination site binds oxygen

sixth

iron

When the what binds oxygen, it moves slightly

protoporphyrin

Upon oxygen binding, the iron moves into the plane of the what ring

histidine

Upon oxygen binding, the iron moves into the plane of the protoporphyrin ring
This also moves what by 0.04 nm

This tiny change results in what binding of oxygen by the other subunits!

cooperative

The movement of the iron moves the histidine, the histidine is part of an what
helix, and the other end of that what helix is near the interface where all the
subunits come together

alpha

conformational

O2 binding to heme in one hemoglobin subunit in the T state triggers a what change to the R state

O2 binding to heme in one hemoglobin subunit in the T state triggers a
conformational change to the R state
The structural change is or is not communicated to the other subunits

is

The two αβ dimers rotate how many ° relative to each other; the other subunits shift into the R state. Some side chain interactions that stabilize the T state break are broken, and new ones that stabilize the R state form

15

The heme in the other what subunits is now more accessible to oxygen

b

oxygen is a what allosteric regulator

homotropic

Functional magnetic resonance can be used to monitor activity in specific regions of the brain by measuring the increase in what

oxyhemoglobin

2,3-bisphosphoglyceric acid (2,3-BPG or BPG)

a small molecule in red blood cells that plays an important role in how hemoglobin binds and delivers oxygen

BPG is a what allosteric modulation

heterotropic

BPG binds in which state to a site distant from the oxygen-binding site

T

BPG when bound, the affinity of hemoglobin for oxygen is greatly what

reduced

the molecule has two phosphate groups and the phosphates are bonded to each other

diphosphate

the molecule has two phosphate groups, not directly connected

bisphosphate

Ionic interactions with BPG stabilize which state

T

Ionic interactions with BPG stabilize the T state
- this makes it harder for what to bind oxygen

deoxyhemoglobin

Ionic interactions with BPG stabilize the T state
- this makes it easier for what with bound oxygen to release it

hemoglobin

The presence of 2,3- BPG allows hemoglobin to convert to the T state and release oxygen when the partial pressure of oxygen does what in tissues

falls

myoglobin

Hemoglobin in the absence of 2,3-BPG behaves like what!

lowered oxygenation of peripheral tissues because hemoglobin binds oxygen less wel

hypoxia

black line

oxygen-binding curve of hemoglobin with no BPG

blue line

oxygen-binding curve of hemoglobin at sea level

over time at high altitudes, BPG levels in the blood what

increases

oxygen-binding curve of hemoglobin with the increased amount of BPG in the blood

green line

Carbon dioxide

What produced by actively respiring cells is taken up by red blood cells

bicarbonate

Carbonic anhydrase in RBCs converts CO2 and water to what and H+

lungs

The bicarbonate is carried to the what in the blood plasma. This is the major way that CO2 is transported to the what to be exhaled

hemoglobin

Carbon dioxide and H+, produced by actively respiring tissues, helps enhance the release of oxygen by what in those tissues

Bohr

The stimulation of oxygen release by carbon dioxide and H+ is called the what effect and has two components

The H+ from actively respiring cells change the local pH from 7.4 to what.

7.2

Lower pH allows the formation of new ionic interactions that stabilize which state

T

the change in pH (from 7.4 to 7.2) due to H+ from actively respiring cells shifts the binding curve of hemoglobin even more to the right

blue curve

Even more O2 is given up at tissues when they are
very active! (gets us to ?% released)

77

Carbon dioxide released by respiring cells reacts with the amino groups of
the hemoglobin chains to form what charged carbamate groups

negatively

T

These carbamate groups also stabilize which state

The stabilization of the T state caused by carbon dioxide from actively respiring cells shifts the binding curve of hemoglobin even more to the what

right

the full Bohr effect (CO2 and H+ effects) results in hemoglobin releasing almost 90% of its bound O2 at actively respiring tissues

purple curve

Carbon dioxide and H+ are which allosteric regulators of hemoglobin

heterotropic

carbon monoxide (CO) binds hemoglobin how many times better than O2

250

CO is a what inhibitor of hemoglobin

competitive