Biosynthesis of Heme
| A |
Glycine |
|
| B | Histidine | |
| C |
Iron |
|
| D |
Folic acid |
Haemoglobin synthesis starts with?
| A |
Glycine |
|
| B |
Histidine |
|
| C |
Iron |
|
| D |
Folic acid |
Ans-A-Glycine
–> Organelle: Partly cytoplasmic and partly mitochondrial
–> Starting materials: Succinyl CoA and Glycine REF: Harper 26th e p. 271-275
Steps of porphyrin ring synthesis:
|
Enzyme |
I Location |
Substrate |
Product |
porphyria |
|
ALA synthase |
Mitochondrion |
Glycine, succinyl CoA |
D-Aminolevulinic acid |
none |
|
ALA dehydratase |
Cytosol |
D-Aminolevulinic acid |
Porphobilinogen |
ALA? Dehydratase deficiency |
|
PBG deaminase Cytosol |
Porphobilinogen |
Hydroxymethyl bilane |
Acute intermittent porphyria |
|
|
Uroporphyrinogen Cytosol III synthase |
Hydroxymethyl bilane |
Uroporphyrinogen III |
Congenital erythropoietic porphyria |
|
|
Uroporphyrinogen Cytosol III decarboxylase |
Uroporphyrinogen III |
Coproporphyrinogen III |
Porphyria cutanea tarda |
|
|
Coproporphyrinogen III oxidase |
Mitochondrion |
Coproporphyrinogen III |
Protoporphyrinogen IX |
Coproporphyria |
|
Protoporphyrinogen oxidase |
Mitochondrion |
Protoporphyrinogen IX |
Protoporphyrin IX |
Variegate porphyria |
|
Ferrochelatase |
Mitochondrion |
Protoporphyrin IX |
Heme |
Erythropoietic protoporphyria |
Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
| A |
Copper |
|
| B |
Tyrosine |
|
| C |
Histidine |
|
| D |
Leucine |
The Beta-chain of Hb begins with valine and histidine. Both these amino acids are important in the synthesis and structure of heamoglobin.
Alignment according to helical designation makes homology evident:
Residue F8 is the proximal heme-linked histidine, and the histidine on the distal side of the heme is E7.
The iron atom is linked by a coordinate bond to the imidazole nitrogen (N) of histidine F8.
The E7 distal histidine, on the other side of the heme plane, is not bonded to the iron atom but is very close to the ligand-binding site.
Ref: Natarajan K., Townes T.M., Kutlar A. (2010). Chapter 48. Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. In J.T. Prchal, K. Kaushansky, M.A. Lichtman, T.J. Kipps, U. Seligsohn (Eds), Williams Hematology, 8e
Along with succinyl CoA which of the following amino acid serve as starting material in heme synthesis?
| A |
Lysine |
|
| B |
Leucine |
|
| C |
Glycine |
|
| D |
Alanine |
- Coproporphyrinogen oxidase catalyze conversion of coproporphyrinogen III to protoporphyrinogen III.
- Protoporphyrinogen oxidase catalyze conversion of protoporphyrinogen III to protoporphyrin III.
- Ferrochelatase catalyze conversion of protoporphyrin III to heme by incorporating heme into protoporphyrin.
All of the following enzymes involved in heme synthesis are found in the mitochondria, EXCEPT:
| A |
Ferrochelatase |
|
| B |
Protoporphyrinogen oxidase |
|
| C |
Coproporphyrinogen oxidase |
|
| D |
Uroporphyrinogen decarboxylase |
- Coproporphyrinogen oxidase catalyze conversion of Coproporphyrinogen III to Protoporphyrinogen III.
- Protoporphyrinogen oxidase catalyze conversion of Protoporphyrinogen III to Protoporphyrin III.
- Ferrochelatase catalyze conversion of Protoporphyrin III to heme by incorporating heme into protoporphyrin.
Which of the following is required in the initial stage of the synthesis of haemoglobin?
| A |
Glycine |
|
| B |
Histidine |
|
| C |
Iron |
|
| D |
Folic acid |
Heme is synthesized in the mitochondria. Starting substances required in the synthesis of heme are succinyl CoA and glycine. Pyridoxal phosphate is required for activation of glycine. Globin the protein part of hemoglobin is synthesized in ribosomes.
Heme synthesis requires
| A |
Ferrous iron |
|
| B |
Glycine |
|
| C |
Succhyl CoA |
|
| D |
All |
Rate limiting step in heme synthesis is catalyzed by ‑
| A |
ALA dehydratase |
|
| B |
ALA synthase |
|
| C |
UPG decarboxylase |
|
| D |
Ferrochelatase |
Ans. is ‘b’ i.e., ALA synthase
Heme is synthesized from ‑
| A |
Lysine + succinyl CoA |
|
| B |
Glycine + succinyl CoA |
|
| C |
Arginine + Malonyl CoA |
|
| D |
Glycine + Malonyl CoA |
Ans. B. Glycine + succinyl CoA
Organelle: Partly cytoplasmic and partly mitochondrial
Starting materials: Succinyl CoA and Glycine
