What is the Heme Biosynthetic Pathway?
Why are some porphyrias in the liver and others erythropoietic?
What does it have to do with hemoglobin?
The heme biosynthetic pathway is one of the key metabolic pathways that leads from the simple building blocks of the amino acid glycine and the dicarboxylic acid succinic acid to the formation first of 5-aminolevulinic acid [ALA], then to the monopyrrole porphobilinogen [PBG], then to porphyrinogens and porphyrins [four pyrrole rings strung together and closed on themselves], and, in the eighth step, to the insertion of an iron atom into the center of the protoporphyrin ring to form heme. Nearly all cells of the human body contain heme, which is essential to carry out many essential functions. Heme functions mainly as a small molecule that binds to proteins to form a large class of proteins called ‘hemoproteins.’ Hemoglobin is one such essential hemoprotein; it is found mainly in developing and adult red blood cells, where it functions to carry oxygen absorbed from air in the lungs to cells and tissue throughout the body. Hemoglobin also functions to carry carbon dioxide, a waste product formed by the metabolic functions of most cells, from these cells back to the lungs, where the carbon dioxide is released into the expired air and where the hemoglobin again picks up more oxygen.
Most of the heme that is synthesized in the human body is made in developing red blood cells, to provide for the formation of heme for hemoglobin. In the erythropoietic porphyrias, the major site of the overproduction of heme precursors is the developing red blood cells. Thus, the name erythropoietic porphyria.
The other major organ where heme is made is the liver. When the major overproduction of heme precursors occurs in the liver, the disorder is called a hepatic porphyria.