Eight steps from glycine and succinyl-CoA to heme, the iron-carrying ring of hemoglobin
Route: Glycine + Suc-CoA → 5-Aminolevulinate → Porphobilinogen → Hydroxymethylbilane → Uroporphyrinogen III → Coproporphyrinogen III → Protoporphyrinogen IX → Protoporphyrin IX → Heme b
The first step, 5-aminolevulinate synthase, needs pyridoxal phosphate: it joins glycine to succinyl-CoA and releases CO₂, which leaves a five-carbon amino ketone. Two of these condense to the pyrrole porphobilinogen. Four porphobilinogens are strung together head to tail into a chain, hydroxymethylbilane, with loss of four ammonia. With the deaminase alone, the ring closes to the symmetric isomer I, which the body does not use. With the cosynthase uroporphyrinogen III synthase, the product is the asymmetric isomer III, the only one used for heme. Uroporphyrinogen decarboxylase removes the carboxyl group from each of the four acetate side chains, which turns them into methyl groups. Coproporphyrinogen oxidase turns two propionate side chains into vinyl groups, and protoporphyrinogen oxidase removes six hydrogens to make the ring system fully conjugated. The last enzyme, ferrochelatase, inserts Fe²⁺ into the center of the ring. In animal cells the first step and the last three happen in the mitochondrion and the middle steps in the cytosol.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | 5-Aminolevulinate synthase | 2.3.1.37 | CoA-SH, CO₂ | |
| 2 | Porphobilinogen synthase (ALA dehydratase) | 4.2.1.24 | H₂O, H₂O | |
| 3 | Hydroxymethylbilane synthase (PBG deaminase) | 2.5.1.61 | H₂O | NH₄⁺, NH₄⁺, NH₄⁺, NH₄⁺ |
| 4 | Uroporphyrinogen III synthase | 4.2.1.75 | H₂O | |
| 5 | Uroporphyrinogen decarboxylase | 4.1.1.37 | CO₂, CO₂, CO₂, CO₂ | |
| 6 | Coproporphyrinogen oxidase | 1.3.3.3 | O₂ | CO₂, CO₂, H₂O, H₂O |
| 7 | Protoporphyrinogen oxidase | 1.3.3.4 | O₂, O₂, O₂ | H₂O₂, H₂O₂, H₂O₂ |
| 8 | Ferrochelatase | 4.98.1.1 | Fe²⁺ |
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).