Biochemical Defects in Two Types of Human Hepatic Porphyria

In a patient with hereditary coproporphyria, increased enzymatic synthesis of δ-aminolevulinic acid (ALA) in the liver contributed to the increased excretion of porphyrins and their precursors. A similar enzymatic abnormality has been found in acute intermittent porphyria. By contrast, in a patient with porphyria cutanea tarda, despite massive porphyrinuria, hepatic ALA synthetase was not detectably elevated. Additional experimental data indicate that heme participates in the feedback regulation of ALA synthetase. Three possible hypotheses describe the defective site of porphyrin biosynthesis in the hepatic porphyrias: a primary increase in ALA synthetase activity; partial blocks in heme biosynthesis; or diversion of heme from its role in the feedback regulation of ALA synthetase.