Heme Flashcards
Where is heme synthesis the highest?
In the bone marrow (for erythropoiesis) and in the liver (for cytochrome formation)
What are the most striking features of heme?
There is an iron ion in the middle surrounded by four interconnected pyrrole rings
Step one of heme synthesis
Succinyl CoA and glycine are combined to form delta-aminolevulinic acid
What catalyzes the first step in heme synthesis?
ALA synthase
What are differences between porphyrinogens and porphyrins?
Porphyrinogens: no double bonds at bridges, colorless
Porphyrins: double-bonded at bridges, colored, fluorescent, and photodegradable
How do porphyrinogens get non-enzymatically oxidized?
Become porphyrins in response to light
How is heme biosynthesis regulated in the liver?
Feedback inhibition by heme on ALA synthase
What are the cells primarily responsible for the degradation of hemoglobin?
Reticuloendothelial system
What are the fates of globin, iron, and porphyrin after degradation of heme?
Globin: broken down into free amino acids
Iron: recycled
Porphyrin: excreted as bile
Heme oxygenase
Breaks down porphyrin into biliverdin
Biliverdin reductase
Reduces biliverdin to bilirubin IX-alpha (indirect bilirubin/unconjugated bilirubin)
How is unconjugated bilirubin carried in the plasma?
As a complex with albumin
How is the albumin-bilirubin complex taken up by the liver?
Through active transport
Describe the process of conjugation of bilirubin in the liver
Glucuronic acid x2 are attached to the unconjugated bilirubin by the propionic side chains
What enzyme catalyzes the reaction of bilirubin conjugation?
Bilirubin UDP glucuronyltransferase
What happens to bilirubin after conjugation?
It is actively secreted into the bile canaliculi
Definition of hyperbilirubinemia
High blood levels of bilirubin (>1 mg/dL)
Definition of jaundice
Diffusion of bilirubin into tissues, making them appear yellow (detectable at serum levels of 2-2.5 mg/dL)
Clinical consequences of hyperbilirubinemia
At concentrations above 25 mg/dL, albumin’s carrying capacity is reached and free unconjugated bilirubin is present in the blood, which can cross the BBB and cause severe central nervous system damage
Hemolysis
Destruction of erythrocytes; causes increase in unconjugated bilirubin
Biliary obstruction
Conjugated bilirubin is not transported back to the liver, and instead spills into blood, causing hyperbilirubinemia. Also causes dark urine and chalky, white stools.
Hepatitis and liver cirrhosis
Decreased conjugation and excretion of bilirubin, causing increase in both conjugated and unconjugated bilirubin.
Neonatal jaundice
Fragile erythrocytes. Decreased conjugation, excretion, and uptake of bilirubin. Causes increase in unconjugated bilirubin.
What is a treatment for neonatal jaundice?
Phototherapy
