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Flashcards in Hemoglobin Deck (57):
1

Where is myoglobin found

found in muscle for oxygen storage

2

Single ferous _____- containng heme prosthetic group in protective hydrophobic pocket binds oxygen

Fe++

3

If oxidized to ferric (Fe+++)

it binds H20

4

what is myoglobins conformation stabilized by

hydrophobic interactions

5

Posterior 93 His (proximal) binds:

Fe++

6

Distal His provides ___ ____ for unfavorable interactions

steric hindrance (CO)

7

What is a heme

4 pyrrole ring structures linked by methene bridges= porphyrin ring

8

When you add specific side groups to a heme its called:

protophorphyrin IX

9

A heme is not considered a heme until you add

Fe++ = heme

10

Where is heme found

oxygen transporter, and storage proteins and cytochromes

11

Myoglobin has ____ alpha helical conformation

75% (8 regions)

12

Myoglobins saturation curve is ____ and is indicative of its function.

hyperbolic; store oxygen until its critically needed

13

Hematopoietic stem cell directed to erythroid lineage by the hormone

erythropoietin

14

Hemoglobin relies on ___ and ___ for energy

glucose and glycolysis

15

Small ___shape allows passage through capillaries

concave

16

Hemoglobin is found in ____ for ____ transport.

RBC's; oxygen

17

Hemoglobin is a tetramer that has 2 ___chains and 2 ___chains. Thus Hb has a quaternary structure and exhibits _____

alpha; beta; cooperativity

18

What are the similarities between Mb and Hb

1. Each has 8 alpha helical regions connected by beta turns.
2. Heme prosthetic group
3. Distal and proximal histidines

19

Hemoglobin is designed to deliver oxygen :

all the time; therefore it has a sigmoidal curve

20

Myoglobin delivers oxygen only when partial pressure of oxygen is:

low; only delivers when need; therefore the curve is hyperbolic

21

What is the embryonic Hb like

zeta and epsilon chains

22

What is fetal Hb like

Adult alpha and fetal Beta like (gamma) are expressed during the 2nd and 3rd trimesters.

23

What is the adult hemoglobin like

2 alpha 2 beta (after 3 months of birth)

24

Hb conformation and oxygen affinity are dependent on 4 environmental variables:

1. pO2
2. pCO2
3. pH
4. 2,3 bisphospho-glycerate concentration

25

What is the Bohr effect

High [H] (low pH), high pC02, and high [2,3 BPG] lower oxygen affinity and shift oxygen saturation curve to the RIGHT --> Enhances delivery of oxygen to metabolically active tissues where C02 and H+ are accumulating

26

High ____ levels such as those in lung capillaries favors oxygen binding and shifts oxygen saturation curve to the ____

pO2 ; left

27

What is CADET, face RIGHT

O2 saturation curve shift to the right and inc O2 delivery in response to increases in:
1. CO2
2. Acid
3. 2, 3 BPG
4. Exercise
5. Temperature

28

Acidic conditions favor ___ ____ between chains to stabilize the deoxy or ___ form of hemoglobin. Oxygenation breaks these bonds, and converts the tetramer to the oxy or relaxed (R) form.

salt bridges; T.

29

___ serves as an acid sensor. Once protonated, it can participate in ionic bonds.

Histidine

30

When heme ____binds oxygen, the ___moves into the plane of the heme group and ulimately causes conformational shifts that break the ionic bonds (salt bridges) and destabilize the ___ form of Hb.

Fe ++; Fe++; deoxy

31

Salt bridge formation favors _____

deoxygenation (Oxygen release)

32

Salt bridge disruption favors ___

oxygenation (oxygen binding)

33

Not all CO2 binds to Hb; most is converted to :

bicarbonate ion by carbonic anhydrase

34

Lungs have a high ____ and drive ___on, whereas they have a low ____ and drive ___off

pO2; oxygen
pC02; CO2

35

Tissues have a high ____ and drive ____. Whereas they have a low _____ and drive ___ off

pCO2; CO2
pO2, O2

36

What is the chloride shift

Each time bicarbonate enters or leaves a RBC, Cl- is pumped in or out in the opposite direction to maintain charge neutrality.

37

BPG interacts with ____charges on ___chain amino termini and stabilizes deoxy Hb.

postive; beta

38

Where do we get 2, 3 BPG?

its a by product of glycolysis; bisphosphoglycerate synthase which is a bifunctional enzyme; feedback inhibited by its end product, 2, 3 BPG

39

When is there an increase of 2, 3 BPG

during alkalosis and hypoxia

40

As you increase altitude, pO2 drops which increases ____ to inc production of RBC's and there is also an inc in ____

EPO, 2, 3 BPG

41

We're almost ____saturated at sea level

100%

42

Salt bridges stabilize ___which delivers oxygen

deoxyhemoglobin

43

Anything decreases oxygen affinity shifts oxygen saturation curve to the:

right

44

Fetal hemoglobin (Hb F) has a higher Oxygen affinity than adult HbA and a slightly diff aa sequence in the region for BPG binding which ____the affinity for 2, 3 BPG which shifts the curve to the

lowers; LEFT

45

In Adult hemoglobin (HbA) BPG interacts with positive charges on ___chain amino termini

beta

46

In fetal hemoglobin (HbF), it acetylates the ___chain so it cant interact with 2,3 BPG and increases oxygen affinity

gamma

47

Abnormal hemoglobin refers to sickle cell hemoglobin; There is a glutamate to ____substitution on the beta chain

valine; which causes hyprophib "sticky spot" on Hb tetramer

48

deoxy HbS tetramers form ___ that precipate in the ___ which deforms cell membrane

fibers; RBC

49

Sickled RBC are fragile with short half life but this property accelerates destruction of ___infected RBS

malaria

50

What is Methemoglobin

an abnormal hemoglobin which occurs when iron in ferrous state (Fe ++) is oxidized to ferric state (Fe+++) and there is insuffucient methemoglobin reductase to reverse this.

51

Ferric state of iron (Fe+++) no longer binds ____ which causes ____

oxygen; cyanosis

52

Which drugs can induce HbM? Which drugs can reduce it back to the ferrous state (Fe++)

procaine; used in dentistry
reducing agents such as ascorbic acid or methylene blue

53

HbM can also be congenital due to substitution of proximal Histidine with _____

tyrosine; only heterozygotes survive

54

What is HbA1c (Glycosolated hemoglobin)

Used as a measure of diabetic control bc glucose in bloodstream will not enzymatically stick to proteins. Hb is in bloodstream so it becomes glycated. It gives the doctor a long term pic of how well their paitient has been controlling their blood glucose levels.

55

What is carbon monoxide Hb

Carbon monoxide binds more avidly to heme Fe++ than oxygen. Once bound, CO inc O2 affinity of remaining tetramer subunits so less O2 is delivered to tissues.

56

How do you treat CO poisoning

put in oxygen chamber with 100% O2 to force replacement. You can die if reach >60% COHb

57

What are the 5 hemoglobin variants

1. HbF (fetal hb0
2. HbM (Methemoglobin)
3. HbS (Sickle cell hemoglobin)
4. HbA1c (Glycosylated Hb)
5. COHb (Carbon monoxide Hb)