Lecture 8-Seidler: Hemoglobin

Question 1

Structure of hemoglobin

Answer 1

• Globin chains

- Porphyrin ring and Fe+2

Question 2

hemoglobin vs myoglobin graph

Answer 2

Myo-hyperbolic and; hemo=sigmoidal

Question 3

Erythropoesis

Answer 3

One cell proliferates to 2,000 cells; 120 lifespan, brutal life d/t squeezing through capillary beds-often call cell remnants. Monitoring RBC structure is a good indication of health.

Question 4

How much heme in hemoglobin?

Answer 4

37% heme in hemoglobin

Question 5

Hemoglobin:

Answer 5

Tetramer- 4 Globin chains…8 total Alpha helices (A-H) alpha 1 and 2 and B 1 and 2 make up the 4 Globin chains,

Question 6

Sickle cell anemia

Answer 6

Substitution from glutamic acid to valine on the 6 helix. This is a nonconservative substitution.

Question 7

Why can’t Hemoglobin be B sheets?

Answer 7

B sheets are sticky and we want to decrease the affinity of the transport molecule to offload O2 into the tissue….not to keep the O2 on the transporter.

Question 8

Embryonic Hemoglobin types:

Answer 8

Zeta and epsilon

Question 9

Fetal hemoglobin types:

Answer 9

Alpha-gamma

Question 10

alpha like chains

Answer 10

Alpha and zeta

Question 11

Beta like chains:

Answer 11

Epsilon, gamma, delta, and Beta

Question 12

Most common adult hemoglobin:

Answer 12

96%: Alpha2Beta2. (Hb A)

4%: alpha2Delta2. (Hb A2)

Question 13

Common fetal hemoglobin type:

Answer 13

Alpha2Gamma2

Question 14

Hemoglobin F

Answer 14

Alpha 2 GAMMA2…should not see after 2 weeks life

Question 15

SHows cooperativity in hemoglobin

Answer 15

Switch and lock: when one binding site removes O2 the rest of the sites will have decreased affinity to remove the O2….same is true for taking up O2….thus, cooperatively, the hemoglobin functions (similar to all or none-protein folding)

Question 16

Ppressure and O2 taken up

Answer 16

W/ inspiration, the Ppressure difference down the gradient pushes the O2 to the hemoglobin(lower pressure)

Question 17

Switch and lock

Answer 17

This is when the helix has conformational change d/t binding or unbinding of O2-15 degree turn.

Question 18

Porphyrin ring:

Answer 18

• Heterocyclic tetrapyrrole; planar and hydrophobic; bound to Globin chain.
• One Fe+2/chain; 4 tetramers civil molecule—O2 binding

Question 19

WHat state is Fe in on Porphyrin ring?

Answer 19

+2….+3 would be a dysfunctional protein…

Question 20

What other molecule can bind to Fe in hemoglobin?

Answer 20

CO and O2 compete for the binding space

Question 21

Proximal Histidine:

Answer 21

F8- this is the 5th coordination site. This is where the Fe+2 ion binds.

Question 22

Distal histidine:

Answer 22

E7: This is the 6th coordination site: this HIS is where O2 will H bond w/ the distal histidine. ALSO FUNCTIONS AS REGULATOR TO KEEP FE+2 TO BECOME FE+3…CONTROLS THE INTRINSIC REACTIVITY OF HEME

Question 23

Hb functions:

Answer 23

Transport Oxygen and CO2 in and out of the body

Question 24

MEchanism of O2 binding:

Answer 24

Fe+2 :O2 binding site, cooperativity, reversible binding, allosteric control

Question 25

Sigmoidal mechanism of O2 dissociation indicates:

Answer 25

Cooperativity

Question 26

During exercise the offloading effects of Hemoglobin can drop by:

Answer 26

66%

Question 27

Cooperativity in Hb

Answer 27

Conformational change in one subunit induces a conformational change in another–inter subunit interactions

Question 28

Structure of myoglobin:

Answer 28

• Myoglobin is a monomer
• one Globin chain-different gene
• one heme-Fe+2

Question 29

Myoglobin has higher affinity b/c:

Answer 29

You want higher O2 affinity in muscle for for mitochondria…final O2 sink…

Question 30

Negative allosteric effectors:

Answer 30

H+(low pH),
CO2, and
2,3-BPG

Question 31

Allosteric control

Answer 31

Bind to distinct sites NOT ACTIVE SITE, induce conformational change to inhibit O2 binding

Question 32

Exercise allows for 66% drop in O2 offloading, but 2,3-BPG w/ exercise allow for:

Answer 32

77% offloading…this makes for more efficient use of the O2…

Question 33

If all three negative allosteric controls are present O2 can drop off to:

Answer 33

88%, Low pH, CO2 elevation and 2,3-BPG controls present

Question 34

Training in the altitudes produces:

Answer 34

Mobilization of hemoglobin in lower affinity state

Question 35

R state

Answer 35

Resting state- oxyhemoglobin state- less constrained

Question 36

T state

Answer 36

Tense state; deoxyhemoglobin; “trying to push O2 out” ; constrained by subunit-subunit interactions.

Question 37

Fetal Hb affinity to maternal:

Answer 37

Higher affinity to remove O2 from maternal Hb. This helps the fetus to obtain O2 from mom.

Question 38

What’s the deal w/ 2,3-BPG and fetal Hb?

Answer 38

Fetal Hb does produce 2,3_BPG, but this sequence is different and is unable to bind in the gamma of Hb F…it is just unable to interact…

Question 39

Switch and lock Mechanism (sequential)

Answer 39

1-O2 binds in 6th position in the pocket of FE+2 and distal His (E7)
2-This pulls Fe+2 into plane of heme
3-Fe+2 movement pulls the proximal histidine (F8)
4-F8 pulls the F helix, and consequently G helix.
5-Sliding of F and G in one complex affects the E helix on other subunit [d/t now being in higher affinity state]

Question 40

Heme is tucked in which helices of Hemoglobin?

Answer 40

EFG