Lecture 7

Question 1

nitric acid (NO)

Answer 1

signaling molecule, helps in delivery of oxygen. also causes vasodilation, inhibition of platelet aggression

Question 2

myoglobin + hemoglobin

Answer 2

approx. 10% of total proteins in the body

Question 3

myoglobin

Answer 3

storage of oxygen in the cytosol, mainly in muscle (gives muscle red color) but also in brown fat

Question 4

hematocrit

Answer 4

40-50% blood volume is red blood cells

Question 5

hemoglobin

Answer 5

contained in red blood cells, transports oxygen from the lungs/gills

Question 6

oxygen transport and storage

Answer 6

hemoglobin transports oxygen from the lungs, delivered to tissues, myoglobin stores it for metabolism by mitochondria, CO2 carried back to lungs and expired

Question 7

nitroglycerin

Answer 7

breaks down release nitric oxide, causes vasodilation of vessels and gets rid of chest pain (angina)

Question 8

bond types in hemoglobin

Answer 8

NOT COVALENT BONDS, forces holding bonds together are ionic, hydrophobic interactions, Van der Waals forces

Question 9

histidine in hemoglobin

Answer 9

crucial for F8 and E7 helices

Question 10

physical characteristics of myoglobin

Answer 10

-extremely compact, 70% of the main chain is alpha helical
-8 major helical segments, all right handed, denoted A-H
- interior consists almost entirely of hydrophobic residues such as leucine, valine, methionine, phenylalanine
- the only charged residues inside Mb are two histidines, critical function at the oxygen binding site
- outside of the protein has both polar and non-polar residues

Question 11

heme

Answer 11

prosthetic portion of myoglobin and hemoglobin

Question 12

ferric iron

Answer 12

when ferrous iron becomes oxidized by dissolved oxygen, can no longer bind more oxygen groups once oxidized

Question 13

ferrous becomes ferric:

Answer 13

Hb becomes methemoglobin
Mb becomes metmyoglobin

Question 14

distal histidine

Answer 14

acts as blocker to oxygen, safely allows oxygen to bind weakly and irreversibly so that ferrous iron is not oxygenated

Question 15

E7 of histidine

Answer 15

blocking role; allows oxygen to bind weakly to ferrous iron preventing oxidation

Question 16

oxygen binding curve for myoglobin

Answer 16

has hyperbolic shape, Mb has one oxygen binding site per molecule, O2 pressure at 50% of Mb= 2mmHg

Question 17

hemoglobin

Answer 17

• 4 polypeptide chains
• weak non-covalent attractions: electrostatic (ionic), hydrogen bonding, hydrophobic, Van der Waals
• in concentrated urea solutions, dissociates into alpha-beta dimers, suggesting strongest contacts are between alpha and beta chains
• adult hemoglobin (HbA1) consists of two alpha chains and two beta chains
  -four oxygen binding sites act in cooperative manner

Question 17

attractions in hemoglobin

Answer 17

electrostatic (ionic), hydrogen bonding, hydrophobic, van der Waals (NO COVALENT)

Question 18

HbA1

Answer 18

adult hemoglobin, consists of two alpha chains and two beta chains

Question 19

each chain contains a ___ group and a ___ oxygen binding site

Answer 19

heme, single

Question 20

amount of oxygen binding sites on hemoglobin

Answer 20

four

Question 21

deoxy conformation

Answer 21

tense or T conformational state

Question 22

oxy conformation

Answer 22

higher O2 affinity, relaxed or R conformational state

Question 23

hemoglobin binding curve

Answer 23

sigmoidal due to cooperative nature
- enables hemoglobin to release more oxygen to the tissues that are in more dire need of oxygen

Question 24

percentage of oxygen tissues get from bound hemoglobin at rest

Answer 24

21

Question 25

percentage of oxygen tissues get from bound hemoglobin during exercise

Answer 25

45

Question 26

binding of the first oxygen molecule to deoxyHb enhances binding of the second molecule by factor of ___

Answer 26

3

Question 27

when 3 oxygen molecules are bound to Hb, the remaining oxygen binding site has an affinity for oxygen ___ times that of the fully deoxygenated Hb

Answer 27

20

Question 28

progressive loss of oxygen molecules from a fully oxygenated Hb ____ the binding of the remaining molecules of bound oxygen

Answer 28

weakens

Question 29

degree of rotation as hemoglobin is oxygenated

Answer 29

15 degrees

Question 30

allosteric effect

Answer 30

uptake of one ligand by a protein influencing the affinities of remaining unfilled binding sites

Question 31

lowers binding affinity of oxygen

Answer 31

hydrogen ions (pH drop), carbon dioxide

Question 32

effects of carbon dioxide on hemoglobin

Answer 32

promote the release of oxygen bound to Hb

Question 33

2,3-diphosphoglycerate

Answer 33

stabilizes deoxy (T) form of Hb and weakens the affinity of Hb for oxygen in red blood cells

Question 34

bohr effect

Answer 34

- facilitates the delivery of oxygen to rapidly metabolizing tissues where carbon dioxide and lactic acid decrease pH - less oxygen a tissue has, the more acidic it becomes. acidity of the tissue allows increase release of oxygen, allowing tissues to receive more oxygen and become less acidic to return to normal state

Question 35

oxygen binding curves for Hb

Answer 35

shift to the RIGHT as pH drops

Question 36

haldane effect

Answer 36

deoxygenated blood can carry more carbon dioxide

Question 37

bisphosphoglycerate (diphosphoglycerate)

Answer 37

-5 charge at pH of 7.4 helps to stabilize deoxy state

Question 38

DPG is ___ when hemoglobin is oxygenated

Answer 38

expelled

Question 39

hemoglobin affinity with 2,3-BPG

Answer 39

- hemoglobin in red blood cells lowers the affinity, favors unloading of oxygen to tissues for respiration, leading to the increase of oxygen delivery from 8% (without) to 66%

Question 40

hemoglobin A1

Answer 40

principal hemoglobin in adults, consists of two alpha chains and two beta chains

Question 41

hemoglobin F

Answer 41

the principal hemoglobin in fetuses, consists of two alpha chains and two gamma chains

Question 42

hemoglobin A2

Answer 42

minor hemoblogin at 2% of total = alpha 2 delta 2

Question 43

fetal Hb vs maternal Hb

Answer 43

- fetal Hb has higher affinity for oxygen than maternal Hb - fetal hemoglobin is able to take up more oxygen - replacement of histidine with serine raies the affinity of fetal hemoglobin, shifting it to the left which favors oxygen loading allowing more oxygen to be delivered to the lungs

Question 44

presence of DPG in fetal Hb

Answer 44

oxygen of fetal Hb is higher than that of maternal hemoglobin

Question 45

cooperativity

Answer 45

loss of oxygen molecules from fully oxygenated R conformation of Hb, destabilizes the R configuration

Question 46

allosteric effectors

Answer 46

H+ (Bohr effect), CO2 (Bohr effect) and DPG act to strengthen the deoxy T conformation (shift curve to the right)

Question 47

strengthening of deoxy conformation (T) shifts binding curve to the right

Answer 47

high CO2, high H+, high T degree, low pH, high DPG

Question 48

strengthening of oxy conformation (R) in remaining oxygen binding sites shifts binding curve to the left

Answer 48

loss of 2 positive charges on fetal Hb (His to Ser), CO binding Fe2+, Fe2+ to Fe3+ methemoglobin at one site