Heme Biosynthesis

Eight-step pathway producing heme from glycine and succinyl-CoA.

Overview

Heme biosynthesis begins in mitochondria with the condensation of glycine and succinyl-CoA by ALA synthase to form δ-aminolevulinic acid (ALA). Subsequent steps alternate between the cytoplasm and mitochondria, proceeding through porphobilinogen, hydroxymethylbilane, uroporphyrinogen III, coproporphyrinogen III, protoporphyrinogen IX, and protoporphyrin IX, with final iron insertion by ferrochelatase.

Cellular Location

Mitochondria and cytoplasm

Clinical Significance

Essential for hemoglobin, myoglobin, and cytochromes; enzyme deficiencies cause porphyrias (acute intermittent porphyria, porphyria cutanea tarda); lead poisoning inhibits ALA dehydratase.

Key Molecules

Glycine Succinyl-CoA δ-Aminolevulinic acid (ALA)Porphobilinogen Uroporphyrinogen III Protoporphyrin IX Heme Fe²⁺

Key Enzymes

ALA synthase (ALAS1/2)ALA dehydratase Porphobilinogen deaminase Uroporphyrinogen decarboxylase Ferrochelatase

Related Pathways

Citric Acid Cycle (Krebs Cycle)

Oxidizes acetyl-CoA to CO₂, generating GTP, NADH, and FADH₂.

Amino Acid Catabolism

Degradation of amino acids to metabolic intermediates and ammonia.