Hemoglobin - Functions and Degradation Flashcards

1
Q

Two forms O2 is transported by in blood, and their percentages

A
Dissolved O2 (<2%)
HbO2 (>98% total blood O2)
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2
Q

product of the pentose phosphate pathway

A

NADPH

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3
Q

What if the concentration of NADPH is low?

A

hemolytic anemia due to too much hemolysis and not enough Hb to carry O2

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4
Q

NADPH produced in RBCs help reduce ____ ______

A

free radicals

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5
Q

a family of chemicals containing cyclic tetrapyrrole

A

porphyrins

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6
Q

Number of heme groups in Mb

A

1

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7
Q

Number of heme groups Hb

A

4

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8
Q

member of the porphyrins family, hydrophobic, contains ferrous iron

A

heme

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9
Q

secondary structure of myoglobin

A

a-helix, 8 regions labelled A-H

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10
Q

tertiary structure of myoglobin

A

globular

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11
Q

Polar residues are on the surface of myoglobin, why?

A

so it can be dissolved in aqueous environments

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12
Q

The interior of Mb contains mostly non-polar amino acids, with hydrophobic interactions packing and stabilizing Mb. Name the two exceptions

A
proximal histidine (His F8)
distal histidine (His E7)
(proximal and distal relative to the heme)
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13
Q

Where is hemoglobin formed?

A

Bone Marrow

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14
Q

How many subunits are in hemoglobin?

A

4

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15
Q

What are the differences between fetal and adult hemoglobin?

A

Adult - HbA1, a2b2

Fetal - HbF, a2y2

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16
Q

Sickle cell Hb mutation

A

HbS, a2d2; point mutation causes cells to stick to blood vessels and rupture

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17
Q

Describe the Hb taut structure and its effects

A

DeoxyHb is constrained by salt bonds among different subunits, thus the binding of the first O2 is difficult

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18
Q

Is binding the 2nd, 3rd, and 4th O2 easier or harder? Why?

A

Easier, accepting the first O2 weaken the salt bonds and lead to conformational changes (R form, relaxed) that facilitate the binding of oxygen

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19
Q

What color is myoglobin under normal conditions?

A

dark red

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20
Q

DeoxyHb color

A

purple-blue, seen during cyanosis

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21
Q

HbO2 color

A

bright red

22
Q

What is produced when Fe2+ in heme is oxidized into Fe3+?

A

methemoglobin (MetHb)

23
Q

What enzyme can convert MetHb back to Hb?

A

methemoglobin reductase

24
Q

What is the color of MetHb? What is the problem with it?

A

MetHb is brown, cannot carry O2

25
Q

Describe what happens when MetHb is abnormally high and what clinical signs may occur as a result?

A

High MetHb –> little Hb available to carry O2 –> impaired tissue perfusion with O2 –> cyanosis and death

26
Q

What are two clinical applications of MetHb toxicosis leading to hypoxia? (Hint: cat and cow)

A

Cat - acetaminophen
Cattle - nitrate poisoning from forage
(both oxidize Fe2+ to Fe3+)

27
Q

The fraction of glycated (glycosylated, HbA1c) Hb is proportional to ______ _______ levels

A

blood glucose

28
Q

normal A1C %

A

3-5%

29
Q

Why is HbA1C a more accurate indicator of average blood glucose levels?

A

Once hemoglobin is glycated, it remains that way until it is catalyzed, approx 8 weeks

30
Q

What is elevated blood [HbA1C] indicative of?

A

poor blood glucose control, such as in diabetes mellitus

31
Q

Increased glycosylation of hemoglobin increases its affinity for oxygen binding, good or bad?

A

Bad, because it will fail to unload O2 to peripheral tissue

32
Q

Describe carbon monoxide toxicity

A

HbCO prevents oxygenation of Hb in the lungs, may bind to cytochromes in the mitochondria, blocking ETC and ATP production

33
Q

Describe cyanide poisoning and its signature clinical presentation

A

CN affects oxidative phosphorylation in cells, decreases utilization of O2, venous blood is still highly oxygenated, causing bright red venous blood

34
Q

where is hemoglobin catabolized? By what cells

A

macrophage/monocyte (MM cells), spleen

35
Q

Describe hemoglobin catabolism within MM cells

A

Globin and heme separated
Globin hydrolyzed to AA
AA can be reused or metabolized in liver ammonia (NH3) –> urea

36
Q

Describe heme catabolism; what happens to ferrous iron? Porphyrin?

A

Iron is stored, reused, or eliminated

Porphyrin is converted into biliverdin

37
Q

How is biliverdin formed? What reaction occurs?

A

Heme oxygenation; Oxidative cleavage of porphyrin ring by heme oxygenase (requires O2 are release CO) to form biliverdin

38
Q

How is bilirubin formed? What enzyme is used?

A

reduction; central methylene bond is reduced by biliverdin reductase to give unconjugated bilirubin (UCB)

39
Q

Is bilirubin hydrophilic or hydrophobic?

A

hydrophobic, not water soluble

40
Q

What is required for bilirubin to be able to be transported in the blood? What is the name of this complex?

A

albumin; albumin-UBC complex

41
Q

Can albumin-UBC complex pass from blood through the glomerular capillary wall into the renal tubular lumen? Why or why not?

A

no, it is too large to pass through, and thus does not enter urine

42
Q

What happens to unconjugated (free) bilirubin after it is is released into the blood by MM cells?

A

it is taken up by hepatocytes in the liver

43
Q

What compound is bilirubin conjugated with in hepatocytes? What product is formed?

A

glucuronic acid

product: bilirubin diglucuronide
enzymes: bilirubin UDP glucuronyltransferase

44
Q

In horses, dogs, cats, mice, and rats, what other compounds may also conjugate with bilirubin? (3)

A

SO4, glucose, xylose

45
Q

How does conjugation change the properties of bilirubin?

A

It adds polar (charged) groups
Increases solubility in water
Facilitates bilirubin elimination

46
Q

Does conjugated bilirubin need to bind to albumin in the blood?

A

no

47
Q

Describe the transport of bilirubin diglucuronide (conjugated bilirubin) into bile

A
  1. Most conjugated bilirubin passes into the intestinal lumen via the biliary system
  2. Some conjugated bilirubin escapes into blood and is taken back up by hepatocytes
48
Q

How much conjugated bilirubin is present in the urine under normal conditions?

A

very little

49
Q

Describe enterohepatic circulation

A

reabsorption of some products by the gut –> portal blood –> pass to liver –> back into the gut

50
Q

Essentially all bilirubin taken up from the blood by hepatocytes is put back in the gut via the ______ _____

A

biliary tract

51
Q

Essentially all “bile pigments” are excreted in the _____

A

feces

52
Q

Unconjugated bilirubin is more likely to cross the blood brain barrier.

A

It has an affinity for brain tissue; albumin is released and UCB passes the blood brain barrier