Chapter 9 Hemoglobin, An Allosteric Protein

Front 1

What is hemoglobin?

Back 1

allosteric protein that displays cooperative binding of molecular oxygen

Front 2

What does the cooperativity of hemoglobin allow?

Back 2

rapid binding of O2 in the lungs and easy release at the tissues

Front 3

Where is O2 required to support metabolism?

Back 3

tissues

Front 4

What is myoglobin?

Back 4

largely alpha-helical protein that binds the prosthetic group heme

Front 5

What does heme consist of?

Back 5

protoprophyrin and a central iron ion

Front 6

organic component with four linked pyrrole rings

Back 6

protoprophyrin

Front 7

What state is the central iron ion of heme in?

Back 7

ferrous (Fe2+)

Front 8

What is the iron ion in heme coordinated to in myoglobin?

Back 8

side chain of a histidine residue referred to as the proximal histidine

Front 9

What does one of the oxygen atoms in O2 bind to?

Back 9

an open coordination site on the iron ion

Front 10

What happens to the iron ion upon oxygen binding?

Back 10

It moves into the plane of the porphyrin.

Front 11

Why does the iron ion move after O2 binds?

Back 11

partial electron transfer from the iron ion to the oxygen atom

Front 12

What does hemoglobin consist of?

Back 12

four polypeptide chains: two alpha and two beta

Front 13

True or false: each of the chains of hemoglobin is similar in amino acid sequence to myoglobin but folds into a different three-dimensional structure.

Back 13

false, similar amino acid sequence and three-dimensional structure

Front 14

How is the hemoglobin tetra best described?

Back 14

pair of alpha beta dimers

Front 15

What is the shape of the oxygen-binding curve for hemoglobin?

Back 15

"S"-like, or sigmoidal

Front 16

What does the sigmoidal shape of the oxygen-binding curve indicate about oxygen binding?

Back 16

That it's cooperative.

Front 17

What significantly increase the efficiency of oxygen transport?

Back 17

cooperative oxygen binding and release

Front 18

What changes about hemoglobin on oxygen binding?

Back 18

quaternary structure

Front 19

How many degrees do the two alpha beta dimers rotate by with respect to each other in the transition from the T to the R state?

Back 19

15

Front 20

What are transmitted to the interface between alpha beta dimers, influencing the T-to-R equilibrium?

Back 20

structural changes at the iron sites in response to oxygen binding

Front 21

What do red blood cells contain in concentrations approximately equal to that for hemoglobin?

Back 21

2,3-bisphosphoglycerate (2,3-BPG)

Front 22

What does 2,3-BPG bind tightly to?

Back 22

T state

Front 23

True or false: stabilizing the T state raises the oxygen affinity of hemoglobin.

Back 23

false

Front 24

Does 2,3-BPG increase or decrease the oxygen affinity of hemoglobin?

Back 24

decrease

Front 25

Why does fetal hemoglobin bind oxygen more tightly than adult hemoglobin?

Back 25

weaker 2,3-BPG binding

Front 26

What allows oxygen transfer from maternal to fetal blood?

Back 26

weaker 2,3-BPG binding

Front 27

What two things are the oxygen-binding properties of hemoglobin markedly affected by and what is this phenomenon called?

Back 27

pH and carbon dioxide

Bohr effect

Front 28

Is the oxygen affinity of hemoglobin increased or decreased by increasing the concentration of hydrogen ions?

Back 28

decreased

Front 29

Is the oxygen affinity of hemoglobin increased or decreased by lowering the pH?

Back 29

decreased

Front 30

Why does lowering pH lower the oxygen affinity of hemoglobin?

Back 30

protonation of the amino termini and certain histidine residues

Front 31

Do protonated residues help stabilize the T or R state?

Back 31

T

Front 32

What does increasing concentrations of carbon dioxide do to the oxygen affinity of hemoglobin?

Back 32

decreases

Front 33

By what two mechanisms do increasing concentrations of carbon dioxide decrease the oxygen affinity of hemoglobin?

Back 33

1. Carbon dioxide is converted into carbonic acid, which lowers the oxygen affinity of hemoglobin by decreasing the pH inside the red blood cell.

2. Carbon dioxide adds to the amino termini of hemoglobin to form carbamates. These negatively charged groups stabilize deoxyhemoglobin through ionic interactions.

Front 34

Why does the Bohr effect help deliver oxygen to sites where it is most needed?

Back 34

because hydrogen ions and carbon dioxide are produced in rapidly metabolizing tissues

Front 35

enhanced activity resulting from synergy between subunits of an allosteric molecule

Back 35

cooperative effect

Front 36

prosthetic group of myoglobin and hemoglobin as well as other proteins

Back 36

heme

Front 37

an organic constituent of the heme prosthetic group

Back 37

protoporphyrin

Front 38

consists of four pyrrole rings joined by methine bridges and contains various side chains

Back 38

protoporphyrin

Front 39

residue occupying the fifth coordination site to which iron can bind in hemoglobin and myoglobin

Back 39

proximal histidine

Front 40

located near the heme group in myoglobin and hemoglobin that helps maintain the heme iron in the Fe2+ oxidation state and inhibits carbon monoxide binding

Back 40

distal histidine

Front 41

allosteric regulator of oxygen binding by hemoglobin

Back 41

2,3-bisphosphoglycertate (2,3-BPG)

Front 42

What is another name for 2,3-BPG?

Back 42

2,3-diphosphoglycerate (2,3-DPG)

Front 43

What is fetal hemoglobin?

Back 43

tetrameric molecule comprising two alpha subunits and two gamma subunits

Front 44

How does the gamma subunit compare to the adult hemoglobin beta subunit?

Back 44

amino acid sequence 72% identical

Front 45

observation that H+ and CO2 promote the release of oxygen from oxyhemoglobin

Back 45

Bohr effect

Front 46

negatively charged group formed between an amino-terminal group and carbon dioxide

Back 46

carbamate

Front 47

What does carbamate do in hemoglobin?

Back 47

Its formation stimulates oxygen release.

Front 48

enzyme abundant in red blood cells that hydrates carbon dioxide in the blood to form bicarbonate (HCO3-)

Back 48

carbonic anhydrase

Front 49

What is HCO3-?

Back 49

bicarbonate, the transport form of carbon dioxide

Front 50

Name three factors that stabilize the deoxy form of hemoglobin.

Back 50

BPG binding

salt bridges between acidic and basic amino acids

salt bridges that include amino-terminal carbamate

Front 51

facilitates the formation of protons and bicarbonate

Back 51

carbonic anhydrase

Front 52

regulation of oxygen binding by hydrogen ions and carbon dioxide

Back 52

Bohr effect

Front 53

binds in the center of the hemoglobin tetramer

Back 53

2,3-biphosphoglycerate

Front 54

results from the change of a single amino acid in the beta chain of hemoglobin

Back 54

sickle-cell anemia

Front 55

oxygen binding component of hemoglobin and myoglobin

Back 55

heme

Front 56

True or false: hemoglobin displays quaternary structure.

Back 56

true

Front 57

composed of four pyrrole rings

Back 57

protoporphyrin

Front 58

amino termini structures that stabilizes the T state

Back 58

carbamate

Front 59

binds the fifth coordinate site in heme

Back 59

proximal histidine

Front 60

True or false: hemoglobin displays tertiary structure only.

Back 60

false, myoglobin

Front 61

What is the physiological significance of the cooperative binding of oxygen by hemoglobin?

Back 61

The cooperatively allows hemoglobin to become saturated in the lungs, where oxygen pressure is high. When the hemoglobin moves to tissues, the lower oxygen pressure induces it to release oxygen and thus deliver oxygen when needed. Thus, the cooperative release favors a more-complete unloading of oxygen in the tissues.

Front 62

When crystals of deoxyhemoglobin are exposed to oxygen, the crystals shatter. Why?

Back 62

Deoxyhemoglobin is in the T state. The presence of oxygen disrupts the R/T equilibrium in favor of the R state. The structural changes are significant enough to cause the crystal to come apart.

Front 63

The oxygen-binding behavior of hemoglobin displays aspects of both the sequential model and the concerted model. Explain.

Back 63

Hemoglobin with oxygen bound to only one of four sites remains primarily in the T-state quaternary structure, an observation consistent with the sequential model. On the other hand, hemoglobin behavior is concerted in that hemoglobin with three sites occupied by oxygen is almost always in the quaternary structure associated with the R state.

Front 64

What accounts for the fact that fetal hemoglobin has a higher oxygen affinity than maternal hemoglobin?

Back 64

Fetal hemoglobin does not bind 2,3-BPG as well as maternal hemoglobin does.

Front 65

What reduces the oxygen affinity of hemoglobin?

Back 65

tightly binding 2,3-BPG

Front 66

What does the presence of 2,3-BPG do?

Back 66

shifts the equilibrium toward the T state

Front 67

What does 2,3-BPG bind to?

Back 67

only the center cavity of deoxyhemoglobin (T state)

Front 68

How is 2,3-BPG expelled, enabling the formation of the R state?

Back 68

size of center cavity decreases

Front 69

What happens to the concentration of 2,3-BPG in a person's red blood cells after that person spends a day or more at high altitude (with an oxygen partial pressure of 75 torr)?

Back 69

increases

Front 70

What effect would an increased concentration of 2,3-BPG have on the oxygen-binding curve for hemoglobin and what does this mean?

Back 70

It would be shifted to the right, promoting the dissociation of oxygen in the tissues and increasing the percentage of oxygen delivered to the tissues.

Front 71

What is a chemical feature of 2,3-BPG?

Back 71

negative charges

Front 72

What happens to the oxygen-dissociation curve of hemoglobin after a decrease in CO2?

Back 72

shifts to the left

Front 73

What happens to the oxygen-dissociation curve of hemoglobin after an increase in 2,3-BPG?

Back 73

shifts to the right

Front 74

What happens to the oxygen-dissociation curve of hemoglobin after an increase in pH?

Back 74

shifts to the left

Front 75

What happens to the oxygen-dissociation curve of hemoglobin after a loss of quaternary structure?

Back 75

shifts way to the left

Front 76

What would be the effect of mutations that placed the BPG-binding site on the surface of hemoglobin?

Back 76

The electrostatic interactions between 2,3-BPG and hemoglobin would be weakened by competition with water molecules. The T state would not be stabilized.