Hemoglobin

Question 1

Hemoglobin

Answer 1

predominant oxygen carrier in the circulatory, tetrameric protein with quaternary structure alpha2beta2 (dimer of alpha beta promoters)

4 subunits (2 alpha and 2 beta), four hemes, 4 O2 binding sites arranged in a tetrahedron

Question 2

Myoglobin

Answer 2

intracellular oxygen transport and storage protein, abundant in vertebrate muscle

8 alpha helices and heme

Question 3

quaternary structure (T vs R)

Answer 3

affects the affinity for O2. O2 binding affects the equilibrium between T and R states. 2 different ways dimers can associate in tetramer.

O2 binding drives T to R conversation

Question 4

Heme

Answer 4

big heterocycle with Fe coordinated in the center. The iron does the business of the heme, binding oxygen.

consists of tetrapyrrole with 4 methyl, 2 vinyl, and 2 propionate substituent groups

Question 5

dexoyHb

Answer 5

hemoglobin with no oxygen bound.

Question 6

proximal histidine

Answer 6

part of hemoglobin that coordinates iron

Question 7

distal histidine

Answer 7

part of hemoglobin that binds to oxygen. increases affinity for oxygen, decreases affinity for carbon dioxide, prevents oxidation of iron.

Question 8

small molecules like CO, NO, and H2S (hydrogen sulfide)

Answer 8

bind heme with greater affinity than oxygen, acting as poisons because they can displace oxygen

Question 9

oxygenation

Answer 9

independent of oxidation. oxygen binds reversibly to Hb in the ferrous state without affecting its oxidation state.

upon oxygenation, a conformational change destabilizes the T state and the bonds get shorter

Question 10

oxidation

Answer 10

refers to whether the iron is iron 2+ (ferrous) or iron 3+ (ferric)

Question 11

P50

Answer 11

pressure at which binding is half maximal, pressure value at which 50% of the maximal O2 load has been released

decreases with greater affinity to oxygen (ex. myoglobin P50 is 2.6 vs hemoglobin P50 is 26 torr)

Question 12

Oxygen disassociation curve of Mb

Answer 12

hyperbolic curve, Mb binds O2 under conditions in which Hb releases it, no T/R transition

buffers the oxygen concentration and increases its transport rate by diffusion within cytoplasm

Question 13

Oxygen disassociation curve of Hb

Answer 13

sigmoidal curve, which reveals cooperative interaction between the oxygen binding sites

loads at 100 torr and releases at 20-30 torr, diffuses through capillaries at 2.5 torr

Question 14

R state

Answer 14

high affinity to oxygen, at high oxygen concentration the dissociation curve is close to the R curve, ex. lungs

Question 15

T state

Answer 15

low affinity to oxygen, at low oxygen concentration the dissociation curve is close to the T curve, easier to unload oxygen, ex. muscles

Question 16

cooperativity

Answer 16

as it gets more oxygen, hemoglobin increases its affinity for oxygen and moves from T state to R state, type of allostery

Question 17

allosteric interaction

Answer 17

a change in 1 binding site affects other binds sites. results in cooperativity of oxygen binding to hemoglobin.

Question 18

positive effectors

Answer 18

O2, increase hemoglobin’s affinity for oxygen, shifts curve left to R state

Question 19

negative effectors

Answer 19

BPG, CO2, H+, Cl-, decrease hemoglobin’s affinity for oxygen, shifts curve right to T state (stabilizes T state, delays T->R transition), promotes unloading of oxygen

Question 20

BPG

Answer 20

unique negative effector, sets midpoint affinity, involved in medium long term acclimation

deoxyHb bound to BPG displays reduced affinity for oxygen. Hb needs BPG to release significant amount of O2.

when Hb moves from T->R state, bonds to BPG are broken

Question 21

purified deoxyHb (stripped)

Answer 21

has much greater oxygen affinity than does hemoglobin in whole blood, due to BPG.

Question 22

acclimation to low O2 pressure

Answer 22

BPG concentration increases to allow more oxygen unloading

Question 23

pH and affinity to Oxygen

Answer 23

high pH (low hydrogen concentration) means Hb has higher affinity for O2 and more O2 is loaded. low pH (high hydrogen concentration) means Hb has lower affinity for O2 and more O2 is loaded.

Question 24

Bohr effect

Answer 24

pH and carbon dioxide concentration are coupled. pH modulates the affinity of hemoglobin but not myoglobin for oxygen.

CO2 lowers pH which lower affinity to oxygen, stabilizing T state of Hb

Question 25

carbonic anyhdrase

Answer 25

accelerates bicarbonate formation which enhances O2 release.

Question 26

fetal hemoglobin

Answer 26

alpha 2 gamma 2, higher affinity for oxygen (pO2 is 15 torr), deoxy-HbF has lower affinity for BPG.