The Chemical Biology of Carbon
Chapter 16: Chemical Biology of the Nitrogen Heterocycle Porphobilinogen in Tetrapyrrole Macrocycle Biosynthesis
Published:05 Apr 2023
The Chemical Biology of Carbon, The Royal Society of Chemistry, 2023, ch. 16, pp. 537-556.
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This final chapter analyzes the chemical logic in the tetrapyrrole biosynthetic pathway to heme B with focus on how the aminomethylpyrrole heterocycle of prophobilinogen is assembled and then utilized to build the tetrapyrrole macrocycles of heme and chlorphyll. Enzymatic steps include the formation of the porphobilinogen building block by aldol condensative dimerization of 4-aminolevulinate, its chain extension to the linear tetrapyrrole hydroxybilane, and its enzyme-directed cyclization to uroporphyrinogen III. Subsequently the tailoring of the macrocycle periphery involves loss of the six of the eight peripheral carboxylates as CO2, six-electron oxidation of the macrocycle to a 20 π-electron system and ferrous iron insertion to give heme B. The aminopyrrole framework of porphobilinogen serves both as electrophile via a C2 azafulvene form and as a nucleophile at C5. Fourteen of the starting 48.