Heme
The oxygen-binding heart of hemoglobin. Heme is an iron-containing porphyrin ring that binds oxygen in red blood cells and enables energy production in mitochondria. Its synthesis is complex, requiring B6, iron, glycine, and succinyl-CoA. Defects in heme synthesis cause porphyrias.
Where Heme Is Found
Hemoglobin
In red blood cells. Four heme groups per molecule. Carries oxygen to tissues.
Myoglobin
In muscle tissue. Stores oxygen for muscle use. One heme per molecule.
Cytochromes
In mitochondria. Electron transport chain. ATP production. CYP450 enzymes.
Catalase
Breaks down hydrogen peroxide. Antioxidant enzyme. Contains heme.
Peroxidases
Thyroid peroxidase makes thyroid hormone. Myeloperoxidase in immune cells.
NOS
Nitric oxide synthase. Makes NO for blood vessels. Contains heme.
Heme Synthesis Requirements
Iron
Central atom inserted last. Iron deficiency = no heme = anemia.
Vitamin B6 (P5P)
ALA synthase cofactor. First step requires B6. Common bottleneck.
Glycine
Amino acid substrate. Combines with succinyl-CoA. Starting material.
Succinyl-CoA
From Krebs cycle. Mitochondrial origin. Combines with glycine.
Copper
Needed for iron insertion enzyme (ferrochelatase). Often overlooked.
Zinc
Some enzymes in pathway need zinc. ALA dehydratase is zinc-dependent.
Heme Synthesis Problems
Porphyrias
Genetic enzyme defects. Intermediates accumulate. Skin, neurological symptoms.
Lead Poisoning
Lead inhibits ALA dehydratase and ferrochelatase. Blocks heme synthesis.
Sideroblastic Anemia
Iron present but can't be incorporated. B6 deficiency can cause. Ring sideroblasts.