Heme biosynthesis pathway showing chemical intermediates and sites of production (mitochondria versus cytosol)

Heme synthesis begins with the formation of delta-aminolevulinic acid (ALA) from glycine and succinyl-CoA by ALA synthase (ALAS); this step is rate-limiting in the liver. Hepatic ALAS is mainly regulated by heme via feedback repression (dashed arrow at the top of the frame). Refer to UpToDate for a discussion of porphyrias that result from deficiencies of these enzymes.