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Flashcards in Heme Metabolism Deck (25)

Where does heme biosynthesis occur?

Heme biosynthesis occurs in most tissues, but is highest in the bone marrow and liver


Heme synthesized in the bone marrow is incorporated into what?



Heme synthesized in the liver is incorporated into what?

cytochromes, particularly cytochrome p450


What are the general structural features of heme?

Porphyrin ring with heme in the middle


Name the two simple molecules that contribute all the atoms for the organic portion of heme.

Succinyl CoA and Glycine


Describe the first step in heme biosynthesis, indicating the product of the reaction and the enzyme responsible

Succinyl CoA + Glycine --> ALA

Catalyzed by ALA synthase


Describe the differences between porphyrinogen intermediates and porphyrins and indicate whether or not porphyrinogens can be non-enzymatically converted to porphyrins

Porphyrinogen: no double bonds at the bridging carbons
Porphyrins: double bonds at the bridging carbons --> colored

Porphyrinogens CAN be non-enzymatically oxidized to porphyrins by light


Describe how heme biosynthesis is regulated in the liver.

increased heme has a negative feedback on the first step in heme synthesis (succinyl CoA + glycine).

This is only true in the liver


What are porphyrias?

Genetic diseases resulting from abnormalities of the enzymes of heme biosynthesis


Indicate which two intermediates of heme biosynthesis are increased in nerve damage



What is the characteristic feature of porphyrias?

Nerve damage


What happens to ALA synthase activity in acute intermittent porphyria?

Increase in ALA synthase activit


Which factors exacerbate acute intermittent porphyria by inducing ALA synthase?

Increased ALA and PBG (porphobilinogen)


Indicate how the feedback inhibition of heme can be used in the treatment of this disease.

Give them straight heme. Heme feedsback negatively on the process and inhibits ALA synthase.


Indicate what causes the photosensitivity seen in many porphyrias

sunlight converts the deposited protoporphyrinogen to porphyrins. The porphyrins are then further degraded by light, a process that generates tissue-destroying singlet oxygen. This leads to blistering and other skin lesions.


Name the cells that are primarily responsible for the degradation of hemoglobin

Catabolism of heme occurs in the phagocytic cells of the reticuloendothelial system (monocyte-macrophage system in the spleen, bone marrow and liver)


Describe the fate of the constituents of hemoglobin: globin, iron and porphyrin

globin: free amino acids
Iron: re-utilized
Porphyrin: degraded


Name the products of porphyrin degradation by heme oxygenase and biliverdin reductase

Heme --> Biliverdin --> Biliruben


Describe how unconjugated bilirubin is carried in the plasma

Unconjugated bilirubin is carried in the plasma as a complex with albumin and is delivered to the liver where it is taken up by active transport and conjugated.


Describe the process of uptake and conjugation of bilirubin and the secretion of conjugated bilirubin by the liver

Bilirubin is conjugated in the liver to UDP-glucuronate in the liver. Conjugated bilirubin is actively secreted into the bile canaliculus. In the intestine, bilirubin diglucuronide is deconjugated by bacterial flora and oxidized to colored stercobilins.


Define hyperbilirubinemia

Elevated bilirubin in serum -- can be either conjugated or unconjugated, or both


Define jaundice

Elevated bilirubin diffuses into the tissues, making them appear yellow.


Describe the clinical consequences of hyperbilirubinemia

Conjugated hyperbilirubinemia is benign. Unconjugated hyperbilirubinemia is benign at low concentrations, but above 25 mg/dL, free unconjugated bilirubin can enter the brain and cause toxic encephalopathy


Describe some causes of hyperbilirubinemia and indicate whether unconjugated or conjugated bilirubin predominates

Hemolysis --> unconjugated
Biliary obstruction --> conjugated
Hepatitis or Cirrhosis --> mixed hyperbilirubinemia


Describe a treatment for neonatal physiological jaundice

Blue light