Heme Synthesis

Heme Synthesis is the biochemical pathway used to create heme, a component of hemoglobin found in red blood cells.

Heme synthesis begins with glycine and succinyl-CoA, which combine to form ALA (aminolevulinic acid), catalyzed by the mitochondrial enzyme, ALA synthase. This is the rate-limiting step of heme synthesis, and it requires the cofactor, Vitamin B6 (Pyridoxine).

Deficiencies in ALA synthase or Vitamin B6 result in sideroblastic anemia. In addition, ALA synthase can be inhibited by high levels of glucose and hemin.

ALA is then converted into porphobilinogen. This reaction is catalyzed by the enzyme ALA dehydratase, which can be inhibited by lead poisoning.

Porphobilinogen is turned into hydroxymethylbilane. This reaction is catalyzed by porphobilinogen deaminase, which is defective in Acute Intermittent Porphyria.

Hydroxymethylbilane is converted into uroporphyrinogen III, which is in turn converted into coproporphyrinogen III. The reaction from uroporphyrinogen into coproporphyrinogen is catalyzed by uroporphyrinogen decarboxylase, which is defective in Porphyria Cutanea Tarda.

Coproporphyrinogen is converted into protoporphyrin, which then undergoes iron chelation by the mitochondrial enzyme, ferrochelatase, producing the end product, heme.The action of ferrochelatase can also be inhibited by lead poisoning.

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