Lecture 8-Seidler: Hemoglobin Flashcards Preview

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Flashcards in Lecture 8-Seidler: Hemoglobin Deck (40)
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1

Structure of hemoglobin

-Globin chains
-Porphyrin ring and Fe+2

2

hemoglobin vs myoglobin graph

Myo-hyperbolic and; hemo=sigmoidal

3

Erythropoesis

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.

4

How much heme in hemoglobin?

37% heme in hemoglobin

5

Hemoglobin:

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,

6

Sickle cell anemia

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

7

Why can't Hemoglobin be B sheets?

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.

8

Embryonic Hemoglobin types:

Zeta and epsilon

9

Fetal hemoglobin types:

Alpha-gamma

10

alpha like chains

Alpha and zeta

11

Beta like chains:

Epsilon, gamma, delta, and Beta

12

Most common adult hemoglobin:

96%: Alpha2Beta2. (Hb A)
4%: alpha2Delta2. (Hb A2)

13

Common fetal hemoglobin type:

Alpha2Gamma2

14

Hemoglobin F

Alpha 2 GAMMA2...should not see after 2 weeks life

15

SHows cooperativity in hemoglobin

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)

16

Ppressure and O2 taken up

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

17

Switch and lock

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

18

Porphyrin ring:

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

19

WHat state is Fe in on Porphyrin ring?

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

20

What other molecule can bind to Fe in hemoglobin?

CO and O2 compete for the binding space

21

Proximal Histidine:

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

22

Distal histidine:

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

23

Hb functions:

Transport Oxygen and CO2 in and out of the body

24

MEchanism of O2 binding:

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

25

Sigmoidal mechanism of O2 dissociation indicates:

Cooperativity

26

During exercise the offloading effects of Hemoglobin can drop by:

66%

27

Cooperativity in Hb

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

28

Structure of myoglobin:

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

29

Myoglobin has higher affinity b/c:

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

30

Negative allosteric effectors:

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