Hemoglobin

Question 1

T/F Oxygen is soluble in water

Answer 1

F, it isn’t that’s why you need hemoglobin

Question 2

Major form of hemoglobin in adults

Answer 2

Hb A

Question 3

Hb A composition

Answer 3

4 polypeptide chains (2 alpha and 2 beta held together via non-covalent interactions)
. Each chain has regions of alpha-helical structure and hydrophobic heme binding pocket

Question 4

Hemoglobin tetramer

Answer 4

Composed of 2 identical dimers, alpha-beta 1 and 2
. Chains in dimer held by hydrophobic interactions
. Dimers held together by polar bonds

Question 5

Deoxyhemoglobin

Answer 5

. T (taut) structure
. 2 alpha-beta dimers interact via ionic and H bonds that constrain movement of polypeptide chain
. Low oxygen affinity form

Question 6

Oxyhemoglobin

Answer 6

. R (relaxed) structure
. Binding of O2 to hemoglobin causes rupture of some polar bonds between alpha-beta dimers allowing movement
. High-oxygen-affinity form

Question 7

T/F there is a small amount of oxygen dissolved in plasma blood

Answer 7

T, but it is physiologically insignificant

Question 8

How many O2 molecules can Hb bind?

Answer 8

4, one at each heme

Question 9

Pulse oximetry

Answer 9

Noninvasive, indirect method of measuring O2 saturation of arterial blood based on light absorption difference by R and T Hb

Question 10

Partial pressure needed to achieve half-saturation of binding sites (P50)

Answer 10

26 mmHg for Hb, 1 mmHg for myoglobin

Question 11

How many O2 molecules can myoglobin carry?

Answer 11

1

Question 12

Myoglobin O2-dissociation curve shape and why

Answer 12

Hyperbolic shape reflecting that myoglobin reversible binds a single molecule of O2

Question 13

What is Mb designed to do?

Answer 13

Bind O2 released by Hb at low pO2 in muscle

. Releases o2 w/in muscle in response for O2 demand

Question 14

When is oxygen dissociation curve Hb steepest and why?

Answer 14

. At O2 concentrations that occur in tissue

. Permits O2 delivery to respond to small changes in pO2

Question 15

What shape O2-dissociation curve for Hb?

Answer 15

Sigmoidal, indicating subunit cooperative binding

. Allows unloading at areas of low pO2

Question 16

Cooperative binding

Answer 16

. Binding of an O2 molecules at 1 heme inc. O2 affinity of remaining heme groups in same tetramer
. Heme-heme interaction

Question 17

Allosteric effectors

Answer 17

. affects the ability of Hb to reversible bind to O2
. PO2
. PH in environment
. PCO2
. 2,3,-BPG
. Bind to one site on Hb and affect binding of O2 to heme groups at other sites on Hb

Question 18

T/F Myoglobin is NOT effected by allosteric effects

Answer 18

T

Question 19

Net effect of structural changes of heme groups

Answer 19

Affinity of Hb for the last O2 bound is 300 times greater than 1st bound O2

Question 20

Where is O2 loaded and unloaded onto Hb

Answer 20

. Loaded in lungs where [O2] is high and Hb is saturated

. Unloaded in peripheral tissues for oxidative metabolism

Question 21

Bohr effect

Answer 21

. Release of O2 from Hb enhanced when pH is lowered/when there is increase pCO2
. Dec. pH and inc. pCO2 shift curve right to stabilize T form
. Inc. pH and dec. pCO2 shift the curve to the left and stabilize R

Question 22

concentration of H and CO2 in capillaries of metabolically active tissues compared with alveolar capillaries of lungs

Answer 22

Concentration is higher in metabolically active tissues than alveolar capillaries where CO2 is released into air

Question 23

Carbonic anhydrase

Answer 23

Coverts CO2 to carbonic acid

CO2 + H2O -> H2CO3 -> spontaneously lose H to become HCO3 + H

Question 24

Major blood buffer

Answer 24

Bicarbonate

Question 25

How does Bohr effect happen?

Answer 25

Ionizable groups (His side chains) that have higher pKa in deoxy Hb than in oxyHb . Inc. in [protons] and decrease in pH causes ionizable groups to be protonated and able to form ionic bonds or salt bridges . Stabilize deoxyHb decreasing O2 affinity

Question 26

When inc. protons and lower pO2 the equilibrium is shifted _____ favoring

Answer 26

Right, deoxyHb

Question 27

When inc. in pO2 or dec. protons, the equilibrium is shifted ____ favoring ____

Answer 27

Left, oxyHb

Question 28

2,3-BPG

Answer 28

. Most abundant organic P in RBCs . Concentration of 2,3-BPG in rbcs is approx. equal to concentration of Hb . Synthesized from intermediate in glycolysis

Question 29

How does 2,3 BPG bind and what does binding do?

Answer 29

. Decreases O2 affinity by binding to T Hb but not R Hb | . Stabilizes T confirmation

Question 30

Where does 2,3-BPG bind?

Answer 30

. Pocket formed by 2 beta-globin chains in center of T form tetramer . Pocket has many pos. Charged amino acids that form ionic bonds w/ Neg. charged P groups on 2,3-BPG

Question 31

How is 2,3-BPG expelled from Hb?

Answer 31

Oxygenation

Question 32

Which does oxygen-dissociation curve move w/ 2,3-BPG

Answer 32

. Presence reduces Hb affinity shifting curve right | . Helps release O2 in tissue partial pressure

Question 33

When does [BPG] inc?

Answer 33

. In response to chronic hypoxia (COPD or high altitudes) | . Chronic anemia

Question 34

How long does it take rbcs to restore depleted 2,3-BPG after being transfused from a bank?

Answer 34

6-24 hours

Question 35

2 ways CO2 is transported as:

Answer 35

. bicarbonate | . Carbamate

Question 36

How is carbamate carried?

Answer 36

. Bound to N-terminal group of Hb forming carbaminoHb | Hb-NH-COO + H

Question 37

How does CO2 affect oxygen dissociation curve?

Answer 37

. Stabilizes T form dec. O2 affinity shifting curve right

Question 38

WHen does CO2 dissociate from Hb?

Answer 38

Released in breath

Question 39

CO binding to Hb

Answer 39

. High affinity . Binds to 1+ heme sites shifting Hb to R conformation and remaining sites bind O2 that don’t have CO . Called carboxyHb . Shifts curve left and changes from sigmoidal to hyperbola . Affect Hb unable to release O2 in tissues

Question 40

How many times greater is CO affinity over O2 affinity?

Answer 40

220 time greater

Question 41

How does CO toxicity result?

Answer 41

. Combo of tissue hypoxia and direct CO-mediated damage at cellular level

Question 42

How is CO toxicity treated?

Answer 42

100% O2 at high pressure to dissociate CO from Hb