Heme Synthesis : Synthesis of Porphyrin Molecule
Heme is a Porphyrin molecule. The porphyrins found in nature are compounds in which various side chains are substituted for the 8 hydrogen atoms numbered in Porphin nucleus. This notes explain about Heme synthesis in animals and plants.
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- Heme is the non-protein part mainly present in that mean which is one of the constituent of Hemoglobin, Chlorophyll, Myoglobin and Cytochromes.
- Heme is a porphyrin nucleous which have tetra pyrrole ring.
- In the structure of heme.
- It contains 4 pyrrole nucleus is connected by methylene bridges
- It is a plannar molecule. The ring contains Vinyl groups(-CH=CH2), Methyl group (-CH3), Propionic acid groups (-CH2-CH2-COOH).
- The biosynthesis of heme mainly takes place partly in Mitochondria and partly in Cytosol of the liver
- The two major sites of heme biosynthesis are Erythroid cells, which synthesizes most of the remainder.
- The synthesis can be explained in several steps.
Steps of Heme synthesis:
Both chlorophyll, the photosynthetic pigment of plants, and heme, the iron protoporphyrin of hemoglobin in animals are synthesized (Heme synthesis) in living cells by a common pathway.
Step 1: Formation of δ-amino Levulinic acid (ALA):
The precursor molecule for the heme synthesis is simplest and non-essential and optically inactive amino acid Glycine and the TCA cycle intermediate Succinyl~coA enzyme. Glycine condenses with Succinyl~coA. It forms δ-amino Levulinic acid. This reaction catalyzed by ALA synthatase. This reaction is takes place in mitochondria. This is the rate limiting step of this pathway.
Glycine + Succinyl~coA → δ-amino Levulinic acid + CO2 + CoenzymeA
Step 2: Formation of Porphyrinogen:
This reaction takes place in Cytosol. The dehydration of two molecules of ALA to form Porphobilinogen by the enzyme ALA dehydrase. The enzyme is inhibited by heavy metal ion lead.
2 (δ-amino Levulinic acid) → Porphobilinogen + H2O
Step 3: Formation of Uroporphyrinogen:
The condensation of four molecules of porphyrinogen. It gives Uroporphyrinogen-III. This reaction catalyzes by Uroporphyrinogen-I synthatase and uroporphyrinogen-III cosynthatase takes place in cytosol.
4 (Phorphobilinogen) →Uroporphyrinogen-III
Step 4: Formation of Heme:
UroPorphyrinogen-III is converted into Heme by a series of decarboxylation and oxidation. Finally the Uro-porphyrinogen-III converted into ProtoPorphyrinogen oxidase. The enzyme ProtoPorphyrin decarboxylase and protoporphyrin oxidase and protoporphyrinogen oxidase. The protoporphyrin-II is modified into heme by substituting the ferrous ion (Fe+3) by the enzyme Ferrochelation.
Uroporphyrinogen-III →→→ Protoporphyrin-IX + 6 Carbondioxide
Protoporphyrin-IX + Fe+3 →HEME