Porphyrin biosynthesis is the enzyme-mediated construction of tetrapyrrole macrocycles through pathways that generate porphyrins and their derivatives. In the mammalian heme pathway, 5-aminolevulinate synthase supplies the initial precursor, and its expression links pathway activity to nutritional regulation [1]. Regulatory interactions can also connect precursor synthesis with the circadian transcriptional system [2]. Maturation of aminolevulinate synthase includes acquisition of its catalytic cofactor, supported by mitochondrial protein machinery. Aminolevulinate dehydratase then condenses precursor molecules into porphobilinogen [3][4]. Successive reactions join four porphobilinogen units into a linear tetrapyrrole and cyclize it to uroporphyrinogen III. Later transformations alter side chains and oxidation state, producing the porphyrin framework that can receive a metal ion during formation of downstream metallated products [5].
- tetrapyrroles
- porphobilinogen
- uroporphyrinogen III
- heme biosynthesis
References
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- Julia R. Kardon; Yvette Y. Yien; Nicholas C. Huston; Diana S. Branco; Gordon J. Hildick-Smith; Kyu Y. Rhee; Barry H. Paw; Tania A. Baker; Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis. Cell 2015, 161, 858-867, 10.1016/j.cell.2015.04.017.
- Gang Liu; Debangsu Sil; Nunziata Maio; Wing-Hang Tong; J. Martin Bollinger; Carsten Krebs; Tracey Ann Rouault; Heme biosynthesis depends on previously unrecognized acquisition of iron-sulfur cofactors in human amino-levulinic acid dehydratase. Nat. Commun. 2020, 11, 1-11, 10.1038/s41467-020-20145-9.
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