L5_Heme Degradation and Metabolism Flashcards
What is the average lifetime of a red blood cell?
120 days
Where is the main location of RBC degradation? what other sites are capable
The spleen, reticular endothelial cells engulf RBCs. liver, bone marrow are also capable.
What is the only part of heme that is recycled?
The iron
What carrier proteins are available to bind free hemoglobin, heme or iron in the blood
Haptoglobin- binds methemoglobin dimers
Hemepexin - Binds free heme
Transferrin- binds free iron
What enzyme converts Heme into Biliverdin? What color is biliverdin. Where does this reaction take place?
Heme oxygenase, its green, occurs in spleen ER. This step releases the iron
What is a natural source of CO in the body?
It is produced when Heme is converted into biliverdin
What is jaundice caused by?
Bilirubin
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?
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.
How is bilirubin made soluble in the liver?
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.
What is crigler najjar syndrome? (what is one possible benefit from this?)
difficiency in Glucuronyl transferase and results in severe jaundice. these people may have less arthlerosclerosis due to more antioxidant activity in the blood.
What happens in neonatal jaundice
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.
What happens to conjugated bilirubin in the intestines?
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.
What color is urobilinogen?
colorless
What does oxidation of urobilinogen cause?
formation of urobilin which contributes to normal color of feces and urine
Describe what happens with prehepatic jaundice
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)
What happens in hepatic jaundice?
Diseased condition of the liver that prevents uptake or conjugation of bilirubin
What happens in posthepatic Jaundice?
Blockage of bile flow out of liver and into intestinal tract. Build up of conjugated bilirubin (pancreatic cancer and gall stones)
How is iron stored? where is iron mainly stored?
Iron is stored in ferritin and hemosiderin (degraded ferritin). The main stores are in the liver, bone marrow, skeletal muscles, and spleen
How is iron transferred back to the bone barrow?
Tansferrin can bind two Fe(3+) ions
What does EDTA do?
It is a metal chelator that acts as an antimicrobial.
Describe the process of iron delivery to the cell in the marrow.
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.
What does direct bilirubin measure?
Conjugated bilirubin
What does total bilirubin measure?
Total bilirubin!
What does indirect bilirubin measure?
Unconjugated= total-conjugated
