Hemoglobin

Question 1

What two blood proteins constitute 95% of blood iron?

Answer 1

Hemoglobin and ferritin

Question 2

List the flow of 02 from the atmosphere and its final form within the body.

Answer 2

bronchi–>lungs–>hemoglobin–>(myoglobin)–>mitochondria–> water

Question 3

The total oxygen content consists of what two types of oxygen?

Answer 3

O2 on Hb (SaO2) + dissolved O2 (PO2)

Question 4

A pale hemoglobin hue may be indicative of :

Answer 4

Anemia

Question 5

A blueish hemoglobin hue may be indicative of :

Answer 5

Cyanosis

Question 6

A yellowish hemoglobin hue may be indicative of :

Answer 6

High [bilirubin] –> jaundice

Question 7

A cherry red hemoglobin hue may be indicative of :

Answer 7

Carbon monoxide poisoning

Question 8

A brownish/blue hemoglobin hue may be indicative of :

Answer 8

Metheglobinemia (chocolate cyanosis).

Question 9

Oxidizing drugs cause the conversion of hemoglobin to metheglobin via what enzyme?

Answer 9

Met-Hb oxidase

Question 10

Lysis of non-functional met-Hb leads to the what changes in blood contents?

Answer 10

An increase in reticulocytes and bilirubin (leading to jaundice) and a decrease in hematocrit.

Question 11

Where does heme/Hb synthesis occur?

Answer 11

Differentiating bone marrow cells

Question 12

What are the normal hematocrit percentages for males vs females?

Answer 12

females: 36-46%
males: 41-53%

Question 13

What is the bodies response to hypoxic renal conditions?

Answer 13

1) release of HIF-1 (Hypoxia inducible factors)
2) Increased release of EPO (erythropoietin)
3) Increase production of RBCs

Question 14

What occurs after aged red blood cells are taken up by the spleen.

Answer 14

Degradation by macrophages and conversion of the biproduct (bilirubin) is converted to Bilirubin di-glucuronide (hydrophobic) to allow release into bile.

Question 15

What are the components of the hemoglobin holoprotein?

Answer 15

Heme: 4 protoporphyrin IX rings + Fe2+
Globin: 2 alpha and 2 beta chains

Question 16

What are the 6 possible covalent binding sites on the heme structure?

Answer 16

4 Nitrogen atoms + a proximal and distal histidine

Question 17

In the carbomonoxy-Hb form, what may be bound to the 6th position of heme?

Answer 17

CO (Carbon monoxide)

Question 18

In the Met-Hb form, what may be bound to the 6th position of heme?

Answer 18

CN- (Cyanide); H20; Cl-

Question 19

In the Cyano Met-Hb form, what may be bound to the 6th position of heme? What is the purpose of this form?

Answer 19

CN-; Met-Hb traps cyanide, marking it for lysis and expulsion by the spleen into bile.

Question 20

What are the allosteric effectors of hemoglobin?

Answer 20

H+
CO2
2,3-BPG
Cl-

Question 21

Name the 3 main forms of adult hemoglobin and their concentrations (%) in the present.

Answer 21

HBA1 - alpha-2, beta-2 -96.8%
HBA2 - alpha-2, delta-2 -2.70%
HBF - alpha-2, gamma-2 -0.47%

Question 22

What is the functional definition of p50?

Answer 22

The [O2] required for 50% saturation of Hb (measure of O2 affinity).

Question 23

The Hill Equation

Answer 23

Y = PO2^nh / (P50^nh) + (PO2^nh)

Question 24

What does the Hill coefficient measure?

Answer 24

degree of cooperative interaction between oxygen binding sites.

Question 25

What are the only 2 charged residues in the interior of normal adult hemoglobin?

Answer 25

His E-7 and F-8

Question 26

When oxygen binds to hemoglobin this leads to a global change. What product is formed and what molecule changes position within the structure?

Answer 26

Oxyhemoglobin; Fe2+

Question 27

In the MWC model, which conformation state is favored per each cooperative binding state?

Answer 27

Oxygen bound: R state favored | Deoxygenated: T state favored

Question 28

How is hemoglobin's high affinity for oxygen when in the R state (O2 bound) overcome?

Answer 28

2,3-BPG stabilizes the T state and lowers affinity

Question 29

When 2,3-DPG is high, what has to occur in order for transition from the T to R state?

Answer 29

High amounts of O2 must be present

Question 30

How does 2,3-BPG affect HbF? Why?

Answer 30

It has much lesser affect, allowing maternal HbA O2 to be released and passed to HbF; HbF is missing a His-143 on the gamma subunit

Question 31

How is deoxyHb T structure stabilized due to high [H+] in the Bohr Effect ?

Answer 31

3 amino acids form 2 salt bridges (require a proton-bound His-146 residue).

Question 32

Where does protonation occur as a result of the Bohr Effect?

Answer 32

His-146; His-122; amino termini ***on alpha chains

Question 33

How does CO2 lower the affinity of hemoglobin for oxygen? What is this called?

Answer 33

Stabilizes deoxyHb by binding amino terminals and forming carbamates (also by causing a pH drop). It is called the Haldane Effect

Question 34

How does chloride promote the formation of the T-state/DeoxyHb?

Answer 34

via interaction with positive deoxyHb side-chains, stabilizing ionic interactions.

Question 35

CO2 bound hemoglobin causes remaining open sites to shift to the _______.

Answer 35

right (O2 affinity decreases)