Hemoglobin Flashcards

1
Q

Where is myoglobin found

A

found in muscle for oxygen storage

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2
Q

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

A

Fe++

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3
Q

If oxidized to ferric (Fe+++)

A

it binds H20

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4
Q

what is myoglobins conformation stabilized by

A

hydrophobic interactions

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5
Q

Posterior 93 His (proximal) binds:

A

Fe++

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6
Q

Distal His provides ___ ____ for unfavorable interactions

A

steric hindrance (CO)

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7
Q

What is a heme

A

4 pyrrole ring structures linked by methene bridges= porphyrin ring

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8
Q

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

A

protophorphyrin IX

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9
Q

A heme is not considered a heme until you add

A

Fe++ = heme

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10
Q

Where is heme found

A

oxygen transporter, and storage proteins and cytochromes

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11
Q

Myoglobin has ____ alpha helical conformation

A

75% (8 regions)

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12
Q

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

A

hyperbolic; store oxygen until its critically needed

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13
Q

Hematopoietic stem cell directed to erythroid lineage by the hormone

A

erythropoietin

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14
Q

Hemoglobin relies on ___ and ___ for energy

A

glucose and glycolysis

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15
Q

Small ___shape allows passage through capillaries

A

concave

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16
Q

Hemoglobin is found in ____ for ____ transport.

A

RBC’s; oxygen

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17
Q

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

A

alpha; beta; cooperativity

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18
Q

What are the similarities between Mb and Hb

A
  1. Each has 8 alpha helical regions connected by beta turns.
  2. Heme prosthetic group
  3. Distal and proximal histidines
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19
Q

Hemoglobin is designed to deliver oxygen :

A

all the time; therefore it has a sigmoidal curve

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20
Q

Myoglobin delivers oxygen only when partial pressure of oxygen is:

A

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

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21
Q

What is the embryonic Hb like

A

zeta and epsilon chains

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22
Q

What is fetal Hb like

A

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

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23
Q

What is the adult hemoglobin like

A

2 alpha 2 beta (after 3 months of birth)

24
Q

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

A
  1. pO2
  2. pCO2
  3. pH
  4. 2,3 bisphospho-glycerate concentration
25
Q

What is the Bohr effect

A

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
Q

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

A

pO2 ; left

27
Q

What is CADET, face RIGHT

A

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
Q

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.

A

salt bridges; T.

29
Q

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

A

Histidine

30
Q

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.

A

Fe ++; Fe++; deoxy

31
Q

Salt bridge formation favors _____

A

deoxygenation (Oxygen release)

32
Q

Salt bridge disruption favors ___

A

oxygenation (oxygen binding)

33
Q

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

A

bicarbonate ion by carbonic anhydrase

34
Q

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

A

pO2; oxygen

pC02; CO2

35
Q

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

A

pCO2; CO2

pO2, O2

36
Q

What is the chloride shift

A

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

37
Q

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

A

postive; beta

38
Q

Where do we get 2, 3 BPG?

A

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

39
Q

When is there an increase of 2, 3 BPG

A

during alkalosis and hypoxia

40
Q

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

A

EPO, 2, 3 BPG

41
Q

We’re almost ____saturated at sea level

A

100%

42
Q

Salt bridges stabilize ___which delivers oxygen

A

deoxyhemoglobin

43
Q

Anything decreases oxygen affinity shifts oxygen saturation curve to the:

A

right

44
Q

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

A

lowers; LEFT

45
Q

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

A

beta

46
Q

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

A

gamma

47
Q

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

A

valine; which causes hyprophib “sticky spot” on Hb tetramer

48
Q

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

A

fibers; RBC

49
Q

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

A

malaria

50
Q

What is Methemoglobin

A

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
Q

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

A

oxygen; cyanosis

52
Q

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

A

procaine; used in dentistry

reducing agents such as ascorbic acid or methylene blue

53
Q

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

A

tyrosine; only heterozygotes survive

54
Q

What is HbA1c (Glycosolated hemoglobin)

A

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
Q

What is carbon monoxide Hb

A

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
Q

How do you treat CO poisoning

A

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

57
Q

What are the 5 hemoglobin variants

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