L5_Heme Degradation and Metabolism Flashcards

1
Q

What is the average lifetime of a red blood cell?

A

120 days

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2
Q

Where is the main location of RBC degradation? what other sites are capable

A

The spleen, reticular endothelial cells engulf RBCs. liver, bone marrow are also capable.

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3
Q

What is the only part of heme that is recycled?

A

The iron

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4
Q

What carrier proteins are available to bind free hemoglobin, heme or iron in the blood

A

Haptoglobin- binds methemoglobin dimers
Hemepexin - Binds free heme
Transferrin- binds free iron

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5
Q

What enzyme converts Heme into Biliverdin? What color is biliverdin. Where does this reaction take place?

A

Heme oxygenase, its green, occurs in spleen ER. This step releases the iron

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6
Q

What is a natural source of CO in the body?

A

It is produced when Heme is converted into biliverdin

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7
Q

What is jaundice caused by?

A

Bilirubin

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8
Q

How is bilirubin produced? what color is it? where is it degraded? how does it get there? what benificial purpose does it serve the body?

A

Biliverdin is reduced by NADPH (biliverdin reductase) in the spleen to bilirubin which is orange/yellow. Bilirubin is poorly soluble but readily diffused through the membrane. It combines with Serum Albumin which increases solubility and carries it to the liver to be degraded. It is a major antioxidant. When it bind an radical it is converted back into biliverdin.

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9
Q

How is bilirubin made soluble in the liver?

A

Glucuronyl bilirubin transferase attached two UDP glucuronic acids to the porpionate groups to form bilirubin diglucuronide or conjugated bilirubin which is then secreted into the bile.

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10
Q

What is crigler najjar syndrome? (what is one possible benefit from this?)

A

difficiency in Glucuronyl transferase and results in severe jaundice. these people may have less arthlerosclerosis due to more antioxidant activity in the blood.

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11
Q

What happens in neonatal jaundice

A

temporary condition due to insufficient production of UDP-glucuronyl transferase. Build up of bilirubin. Phototherapy helps break down the bilirubin into soluble products that the liver can digest.

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12
Q

What happens to conjugated bilirubin in the intestines?

A

Intestinal bacteria convert it to a series of urobilinogens, a small amount of which can be found in the plasma due to reabsorption. these are generally secreted back into bile or processed by the kidneys.

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13
Q

What color is urobilinogen?

A

colorless

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14
Q

What does oxidation of urobilinogen cause?

A

formation of urobilin which contributes to normal color of feces and urine

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15
Q

Describe what happens with prehepatic jaundice

A

Massive breakdown of RBS resulting in over production of free bilirubin. liver cells cannot conjugate at the rate bilirubin enters and thus free bilirubin builds up (not necessarily a problem with the liver)

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16
Q

What happens in hepatic jaundice?

A

Diseased condition of the liver that prevents uptake or conjugation of bilirubin

17
Q

What happens in posthepatic Jaundice?

A

Blockage of bile flow out of liver and into intestinal tract. Build up of conjugated bilirubin (pancreatic cancer and gall stones)

18
Q

How is iron stored? where is iron mainly stored?

A

Iron is stored in ferritin and hemosiderin (degraded ferritin). The main stores are in the liver, bone marrow, skeletal muscles, and spleen

19
Q

How is iron transferred back to the bone barrow?

A

Tansferrin can bind two Fe(3+) ions

20
Q

What does EDTA do?

A

It is a metal chelator that acts as an antimicrobial.

21
Q

Describe the process of iron delivery to the cell in the marrow.

A

Ferro-transferin binds its receptor on the cell surface and is endocytosed. the pH of the endosome drops to 5. Fe is released. The vesicle is then exocytosed where the Apotransferrin dissociated from the receptor.

22
Q

What does direct bilirubin measure?

A

Conjugated bilirubin

23
Q

What does total bilirubin measure?

A

Total bilirubin!

24
Q

What does indirect bilirubin measure?

A

Unconjugated= total-conjugated

25
Q

What are two causes of post-hepatic jaundice?

A

Pancreatic cancer and gall stones.

26
Q

where is transferrin made?

A

Liver

27
Q

What 2 things does heme oxidase need to convert heme into biliverdin?

A

O2 and NADPH