Heme synthesis

Question 1

Cyclic compounds formed by the linkage of four pyrrole rings through methyne bridges

Answer 1

Porphyrins

Question 2

Porphyrins form complexes with ____

Answer 2

Metal ions bound to nitrogen atom of the pyrrole rings

Question 3

Site of heme synthesis

Answer 3

• Tissue/organ
  
  • is present in almost all tissues because heme proteins are used in:
    
    • Hemoglobin and myoglobin
    • Cytochromes
    • Enzymes
• Subcellular
  
  • Both cystosol and mitochondria

Question 4

Responsible for the rate-limiting step of heme synthesis

• Reaction
• Enzyme

Answer 4

• Reaction
  
  • Glycine + succinyl-Co-A → aminolevulinic acid
• Enzyme
  
  • δ-ALA synthase

Question 5

What cofactor is necessary for the rate-limiting step in heme synthesis?

Answer 5

Vitamin B6, which is needed to convert glycine and succinyl-Co-A to aminolevulinic acid

Question 6

Which step in heme synthesis requires iron?

Answer 6

The final step, where protoporphyrin is converted to heme by ferrochelatase

• Memory aid:*
• You need ferrous (iron) so ferrochelatase could convert protoporphyrin to heme

Question 7

How does heme provide negative feedback for its own synthesis?

Answer 7

Heme inhibits ALA dehydratase, the second step in heme synthesis

Question 8

Intermediates in heme synthesis

Answer 8

Glycine + succinyl-CoA

↓

Aminolevulinic acid

↓

Porphobilinogen

↓

Uroporphyrinogen

↓

Coproporphyrinogen

↓

Protoporphyrin (Protoheme)

↓

Heme

• Memory aid:*
• Get Some Ala Placed in Urine Cup to Produces Heme

Question 9

Glycine + succinyl-CoA

↓

Aminolevulinic acid

• Enzyme
• Disease associated with problem in enzyme

Answer 9

• Enzyme
  
  • Aminolevulinate synthase (rate-limiting step)
• Disease associated with problem in enzyme
  
  • Sideroblastic anemia (X-linked)

Question 10

Aminolevulinic acid

↓

Porphobilinogen

• Enzyme
• Disease associated with problem in enzyme

Answer 10

• Enzyme
  
  • ALA dehydratase
• Disease associated with problem in enzyme
  
  • Lead poisoning or heavy metals because they replace the zinc

Summary:

• Step 1: glycine + succinyl-CoA → ALA by ALA synthase
• Step 2: Condensation of 2 ALA by zinc-containing ALA dehydratase
• Memory aid:*
• Step 2 uses 2inc by condensing 2 ALAs

Question 11

Porphobilinogen

↓

Uroporphyrinogen

• Enzyme
• Disease associated with problem in enzyme

Answer 11

• Enzyme
  
  • Porphobilinogen deaminase
• Disease associated with problem in enzyme
  
  • Acute intermittent porphyria

Memory aid:

• _U_roporphyrinogen
• ac_U_te intermittent porphyria

Question 12

Uroporphyrinogen

↓

Coproporphyrinogen

• Enzyme
• Disease associated with problem in enzyme

Answer 12

• Enzyme
  
  • Uroporphyrinogen decarboxylase
• Disease associated with problem in enzyme
  
  • Porphyria cutanea tarda

Memory aid:

• _C_oproporphyrinogen
• porphyria _C_utanea tarda

Question 13

Protoporphyrin (Protoheme)

↓

Heme

• Enzyme
• Added substrate
• Disease associated with problem in enzyme

Answer 13

• Enzyme
  
  • Ferrochelatase
• Added substrate
  
  • Iron
• Disease associated with problem in enzyme
  
  • Lead poisoning
• Note:*
• Introduction of iron occurs spontaneously, but the rate is enhanced by ferrochelatase that is also inhibited by lead