tetrapyrrole

Tetrapyrroles are a class of heterocyclic macrocycles consisting of four pyrrole rings linked by methine bridges to form an extended conjugated system. The core macrocycle, often called a porphyrin ring, can coordinate a metal ion at its center to form metalloporphyrins. Common biological examples include heme (iron) and chlorophyll (magnesium); related systems include siroheme and the corrin ring of cobalamin (vitamin B12), a structurally related but partially reduced tetrapyrrole.

These molecules are typically planar and highly conjugated, lending them distinctive electronic and photophysical properties. Substitution on the periphery and varying oxidation states yield a family of pigments and cofactors with diverse roles in biology. The central metal ion is essential for function, governing redox activity and reactivity in the associated enzyme or photosynthetic complex.

Biosynthesis starts with the formation of 5-aminolevulinic acid (ALA) from glycine and succinyl-CoA (in animals) or via the C5 pathway in plants and many bacteria. Four ALA units are condensed to form porphobilinogen, which is linked and cyclized to yield uroporphyrinogen III. Oxidation and side-chain modifications produce protoporphyrin IX; insertion of Fe2+ by ferrochelatase yields heme. In plants, magnesium is inserted by magnesium chelatase to form chlorophyll precursors, followed by tailing and further modifications.

Tetrapyrroles are essential cofactors in respiration and photosynthesis, participate in various catalytic processes, and contribute to disease when biosynthesis is defective. Porphyrias are clinical disorders arising from disruptions in heme synthesis. The chemistry of tetrapyrroles also underpins applications in medicine and diagnostics, including photodynamic therapy and imaging.