Hemoglobin

Question 1

Hemoglobin is an allosteric oxygen-binding protein. What does this mean?

Answer 1

Allosteric- combines at another site, not at the active site

- The cooperative binding is due to this effect, binding to one site affects the binding at another site*

Question 2

Main task of hemoglobin?

Answer 2

1. Carry oxygen from the lungs to tissue for cellular respiration
2. It consists of 4 subunits total:
   - 2 alpha subunits (141 amino acids each)
   - 2 beta subunits (146 amino acids each)

Therefore, it is a tetramer (tetra=four)
Each subunits contains a heme moiety which can bind 1 oxygen

Question 3

A single hemoglobin molecule can bind up to _________ oxygen molecules

Answer 3

4

Question 4

When hemoglobin binds to oxygen, what happens to the subunits?

Answer 4

1. Slightly shift and a conformational change occurs

Question 5

Note the conformation difference between oxy and deoxyhemoglobin including the size of the cleft?

Answer 5

1. Cleft gets smaller in oxyhemoglobin

Question 6

Oxygen molecules bind to hemoglobin in a _________ fashion

Answer 6

1. Cooperative Fashion
   - the first oxygen bind to hemoglobin with the lowest affinity
   - each successive oxygen binds with higher affinity
   - initially hemoglobin is reluctant to take up oxygen, but oxygen affinity increases with each oxygen molecule uptake
   - this causes oxygen uptake curve to be sigmoidal (s shaped)

Question 7

In the lung, where oxygen tension is relatively high, what happens to hemoglobin?

Answer 7

1. It is nearly saturated with oxygen

Question 8

In deep tissues where oxygen tension is low, what happens to hemoglobin?

Answer 8

1. It releases half of its oxygen

Question 9

Ligation of protoporphyrin IX with an iron atom (Fe) results in the formation of what?

Answer 9

1. Heme
   - Note that the 4 bonds to Fe are to the nitrogens (coordination site) of the protoporphyrin group
   - in hemoglobin, the 5th Fe bond is to a histidine residue in the protein portion, the 5th coordination site
   - When O2 is present, it binds to the 6th coordination site of Fe

Question 10

What charge does Heme have?

Answer 10

+2 charge, positive charge

Question 11

Deoxyhemoglobin

Answer 11

1. Fe 2+ is not bound in deoxy form, but will bind O2 and CO when each is present
2. Ferrous iron- no ligand on 6th site of iron

Question 12

Oxyhemoglobin

Answer 12

1. Ferrous iron is bound to oxygen

2. After one O2 is bound, others bind more readily because of conformational change

Question 13

Carboxyhemoglobin

Answer 13

1. Ferrous iron is bound to CO

- this forms a stronger bond that with O2

Question 14

Methemoglobin

Answer 14

1. The iron is in the ferric form and will not bind to O2 or CO.
2. Oxidation of Fe 2+ to Fe 3+ is caused by oxidants such as chlorite S, nitrates, NO

Question 15

Fe++ or Fe 2+

Answer 15

Ferrous iron

Question 16

Fe +++ or Fe +3

Answer 16

Ferric iron (non functional hemoglobin)

Question 17

Sulfmethemoglobin

Answer 17

Fe 3+ — SH
Rare, in H2S toxicity, blood is purple to green color
Can occur due to medication

Question 18

Cyanmethemoglobin

Answer 18

Fe 3+ —– CN
Occurs in cyanide poisioning
Iron must be ferric before it will bind to CN
This property of methemoglobin an be used in cyanide poisioning to sequester CN
Has negative charge

Question 19

Fetal Hemoglobin

Answer 19

1. Differences in protein portion
2. Normally present in fetus before birth, it has slightly higher affinity for O2 than adult hemoglobin (left shift)
3. Mother nature making sure baby is taken care of before the mother

Question 20

Oxygen Saturation

Answer 20

Percentage based on volume

SaO2= [Blood oxygen content (ml/dl)/ blood oxygen capacity (ml/dl)]X 100

Question 21

SaO2 refers to _______ oxygen in red blood cells

Answer 21

Arterial oxygen
Small amount of dissolved oxygen is substrated
SaO2 is independent of the amount of Hb present or forms of Hb present

Question 22

Blood oxygen content equation

Answer 22

1. Concentration of Hb X % saturation of hemoglobin + O2 solubilized in the plasma

Equation:
Oxygen content (ml/dl)= Hb (g/dl) X So2 X 1.34 (ml/g) + (.003 x Po2)

Question 23

SO2

Answer 23

Percentage of oxygen saturation (%)

Question 24

PO2

Answer 24

Partial pressure of oxygen (mmHg)

Question 25

1.34

Answer 25

Molar oxygen capacity of Hb (ml O2 bound at full saturation)

Question 26

.003

Answer 26

Solubility coefficient of oxygen in plasma (ml/dl/mmHg)

Question 27

Blood Oxygen Content in "Volumes Percent"

Answer 27

1. A normal person has about 15 grams of hemoglobin/100 ml of blood 2. Each gram of Hb can bind a maximum of 1.34 ml of O2

Question 28

On average, the hemoglobin in 100 ml (dl) of blood can bind up to ______ ml of O2?

Answer 28

1. 20 ml | 2. 20 ml of O2/dl blood= 20%

Question 29

PO2 and Volume % in Oxygen in Blood

Answer 29

1. FUll saturatio= 20% 2. The effect of PO2 on the quantity of oxygen bound w/ hemoglobin in blood 3. Note: in normal venous blood hemoglobin has released not more than half of the oxygen 4. Sigmoid curve

Question 30

Right shift of Oxygen-hemoglobin dissociation curve- what does it mean and what causes this?

Answer 30

1. Right shift= hemoglobin has less affinity for oxygen 2. Shift to the right is caused by: increased H ions, increased CO2, increased temperature, increased 2,3 DPG, a metabolic product. DPG binds to the enlarged cleft of deoxyhemoglobin The effect of H+, CO2, and DPG favors release of oxygen in tissues where it is needed

Question 31

Shift to right vs shift to left of oxygen-hemoglobin dissociation curves and P50?

Answer 31

1. Shift to right- hemoglobin has less affinity for oxygen. Need to put more oxygen into the system (causes- rise in 2, 3 DPG, rise in temp, increase in H+ and CO2) 2. Shift to left: more affinity for oxygen. (Causes- fall of 2, 3 DPG, fall of temp, fall of H+ ions)

Question 32

Bohr Effect

Answer 32

1. Effect of carbon dioxide and hydrogen ions to shift the oxygen-hemoglobin dissociation curve

Question 33

Carbon Monoxide-Hemoglobin Binding Curve

Answer 33

1. Very low pressure at which CO will bind to hemoglobin 2. CO has about a 200 times greater affinity for hemoglobin than O2 3. The Oxygen p50 of arterial blood is about 27 mmHg 4. Once CO is bound to hemoglobin- very hard to get it off

Question 34

Arterial vs venous ph normal:

Answer 34

1. Arterial= 7.35-7.45 | 2. Venous= 7.32-7.42

Question 35

Arterial vs Venous PCO2 normal:

Answer 35

1. Arterial: 35-45 mmhg | 2. Venous: 41-51 mmhg

Question 36

PO2 normal arterial vs venous

Answer 36

Adults arterial: 80-100 mmhg Adults venous: 25-40 mmhg Over 65 arterial: 75-85 mmHg Newborn arterial: 60-70 mmHg

Question 37

O2 content for men vs women?

Answer 37

Men: 17.5-23 vol % Women: 16-21.5 vol %

Question 38

Normal P50

Answer 38

27 mmHg