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
Describe what happens when MetHb is abnormally high and what clinical signs may occur as a result?
High MetHb --> little Hb available to carry O2 --> impaired tissue perfusion with O2 --> cyanosis and death
26
What are two clinical applications of MetHb toxicosis leading to hypoxia? (Hint: cat and cow)
Cat - acetaminophen Cattle - nitrate poisoning from forage (both oxidize Fe2+ to Fe3+)
27
The fraction of glycated (glycosylated, HbA1c) Hb is proportional to ______ _______ levels
blood glucose
28
normal A1C %
3-5%
29
Why is HbA1C a more accurate indicator of average blood glucose levels?
Once hemoglobin is glycated, it remains that way until it is catalyzed, approx 8 weeks
30
What is elevated blood [HbA1C] indicative of?
poor blood glucose control, such as in diabetes mellitus
31
Increased glycosylation of hemoglobin increases its affinity for oxygen binding, good or bad?
Bad, because it will fail to unload O2 to peripheral tissue
32
Describe carbon monoxide toxicity
HbCO prevents oxygenation of Hb in the lungs, may bind to cytochromes in the mitochondria, blocking ETC and ATP production
33
Describe cyanide poisoning and its signature clinical presentation
CN affects oxidative phosphorylation in cells, decreases utilization of O2, venous blood is still highly oxygenated, causing bright red venous blood
34
where is hemoglobin catabolized? By what cells
macrophage/monocyte (MM cells), spleen
35
Describe hemoglobin catabolism within MM cells
Globin and heme separated Globin hydrolyzed to AA AA can be reused or metabolized in liver ammonia (NH3) --> urea
36
Describe heme catabolism; what happens to ferrous iron? Porphyrin?
Iron is stored, reused, or eliminated | Porphyrin is converted into biliverdin
37
How is biliverdin formed? What reaction occurs?
Heme oxygenation; Oxidative cleavage of porphyrin ring by heme oxygenase (requires O2 are release CO) to form biliverdin
38
How is bilirubin formed? What enzyme is used?
reduction; central methylene bond is reduced by biliverdin reductase to give unconjugated bilirubin (UCB)
39
Is bilirubin hydrophilic or hydrophobic?
hydrophobic, not water soluble
40
What is required for bilirubin to be able to be transported in the blood? What is the name of this complex?
albumin; albumin-UBC complex
41
Can albumin-UBC complex pass from blood through the glomerular capillary wall into the renal tubular lumen? Why or why not?
no, it is too large to pass through, and thus does not enter urine
42
What happens to unconjugated (free) bilirubin after it is is released into the blood by MM cells?
it is taken up by hepatocytes in the liver
43
What compound is bilirubin conjugated with in hepatocytes? What product is formed?
glucuronic acid product: bilirubin diglucuronide enzymes: bilirubin UDP glucuronyltransferase
44
In horses, dogs, cats, mice, and rats, what other compounds may also conjugate with bilirubin? (3)
SO4, glucose, xylose
45
How does conjugation change the properties of bilirubin?
It adds polar (charged) groups Increases solubility in water Facilitates bilirubin elimination
46
Does conjugated bilirubin need to bind to albumin in the blood?
no
47
Describe the transport of bilirubin diglucuronide (conjugated bilirubin) into bile
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
How much conjugated bilirubin is present in the urine under normal conditions?
very little
49
Describe enterohepatic circulation
reabsorption of some products by the gut --> portal blood --> pass to liver --> back into the gut
50
Essentially all bilirubin taken up from the blood by hepatocytes is put back in the gut via the ______ _____
biliary tract
51
Essentially all "bile pigments" are excreted in the _____
feces
52
Unconjugated bilirubin is more likely to cross the blood brain barrier.
It has an affinity for brain tissue; albumin is released and UCB passes the blood brain barrier