Porphyrinogens that leak into extracellular fluid undergo auto-oxidation and are excreted primarily as porphyrins. But please note that appreciable amounts of unoxidized coproporphyrinogen may be excreted in urine. If they accumulate in bone marrow or liver they appear in plasma, are taken up by the liver, and are excreted in bile and feces. Heme is synthesized in largest amounts by the bone marrow, where it is incorporated into hemoglobin, which is an oxygen transport protein, and by the liver, where most is incorporated into cytochromes, which are electron transport proteins. The most abundant cytochromes in liver are the cytochrome P-450 enzymes that metabolize drugs and many other foreign and endogenous chemicals.
Heme biosynthesis is managed differently in liver than in the bone marrow.
Hepatic heme biosynthesis is rate-limited and primarily regulated by the first enzyme, ALA synthase. Certain drugs and hormones induce hepatocytes to make more ALA synthase, heme, and cytochrome P-450. In the bone marrow, heme is made in erythroblasts and reticulocytes that still contain mitochondria, whereas circulating erythrocytes lack mitochondria and cannot form heme. Bone marrow cells express erythroid-specific forms of some pathway enzymes. The authors of much of the material on Porphyria in this medical text is by the world reknown porphyria researchers Kappas and Sassa.