Substrates and Enzymes of the Heme Biosynthetic Pathway and the Diseases Associated With Their Deficiency
Substrate/Enzyme* | Porphyria | Neurovisceral Symptoms | Cutaneous Symptoms | Inheritance |
|---|---|---|---|---|
Glycine+ succinyl coenzyme A † | X-linked protoporphyria (due to increased enzyme activity) † | No | Phenotypically similar to erythropoietic protoporphyria | X-linked |
Delta-aminolevulinic acid | ALAD-deficient porphyria | Yes | No | Autosomal recessive |
Porphobilinogen Porphobilinogen deaminase (also called hydroxymethylbilane synthase) | Acute intermittent porphyria | Yes | No | Autosomal dominant |
Hydroxymethylbilane Uroporphyrinogen III cosynthase | Congenital erythropoietic porphyria | No | Severe, mutilating skin disease | Autosomal recessive |
Uroporphyrinogen III Uroporphyrinogen decarboxylase | Porphyria cutanea tarda | No | Fragile skin, blisters, bullae | Two variants:
|
Hepatoerythropoietic porphyria | No | Severe blistering from infancy; often disfiguring | Autosomal recessive | |
Coproporphyrinogen III Coproporphyrinogen oxidase | Hereditary coproporphyria | Yes | Fragile skin, blisters | Autosomal dominant |
Protoporphyrinogen IX Protoporphyrinogen oxidase | Variegate porphyria | Yes | Fragile skin, blisters | Autosomal dominant |
Protoporphyrin IX Ferrochelatase | Erythropoietic protoporphyria | No, except in patients with severe hepatobiliary pathology | Skin pain, swelling, redness; lichenification and other minor skin changes, but no blistering | Autosomal recessive |
Heme (final product incorporated in various heme proteins) | — | — | — | — |
* Listed are successive intermediates in the heme biosynthetic pathway, beginning with glycine and succinyl CoA and ending with heme. Deficiency of an enzyme causes buildup of precursor compounds. | ||||
† X-linked protoporphyria results from gain-of-function mutations that increase the activity of ALAS 2, causing accumulation of protoporphyrin. Decreased activity of ALAS 2 causes a sideroblastic anemia. | ||||