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Porphyrin and Heme Metabolism and the Porphyrias

  1. Herbert L. Bonkovsky1,2,3,
  2. Jun-Tao Guo4,
  3. Weihong Hou1,
  4. Ting Li1,
  5. Tarun Narang1,
  6. Manish Thapar5

Published Online: 1 JAN 2013

DOI: 10.1002/cphy.c120006

Comprehensive Physiology

Comprehensive Physiology

How to Cite

Bonkovsky, H. L., Guo, J.-T., Hou, W., Li, T., Narang, T. and Thapar, M. 2013. Porphyrin and Heme Metabolism and the Porphyrias. Comprehensive Physiology. 3:365–401.

Author Information

  1. 1

    Departments of Medicine and Research and The Liver-Biliary-Pancreatic Center, Carolinas Medical Center, Charlotte, North Carolina

  2. 2

    Department of Medicine, University of Connecticut, Farmington, Connecticut

  3. 3

    Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

  4. 4

    Department of Bioinformatics and Genomics, College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, North Carolina

  5. 5

    Department of Medicine, Drexel University, Philadelphia, Pennsylvania

Publication History

  1. Published Online: 1 JAN 2013

Abstract

Porphyrins and metalloporphyrins are the key pigments of life on earth as we know it, because they include chlorophyll (a magnesium-containing metalloporphyrin) and heme (iron protoporphyrin). In eukaryotes, porphyrins and heme are synthesized by a multistep pathway that involves eight enzymes. The first and rate-controlling step is the formation of delta-aminolevulinic acid (ALA) from glycine plus succinyl CoA, catalyzed by ALA synthase. Intermediate steps occur in the cytoplasm, with formation of the monopyrrole porphobilinogen and the tetrapyrroles hydroxymethylbilane and a series of porphyrinogens, which are serially decarboxylated. Heme is utilized chiefly for the formation of hemoglobin in erythrocytes, myoglobin in muscle cells, cytochromes P-450 and mitochondrial cytochromes, and other hemoproteins in hepatocytes. The rate-controlling step of heme breakdown is catalyzed by heme oxygenase (HMOX), of which there are two isoforms, called HMOX1 and HMOX2. HMOX breaks down heme to form biliverdin, carbon monoxide, and iron. The porphyrias are a group of disorders, mainly inherited, in which there are defects in normal porphyrin and heme synthesis. The cardinal clinical features are cutaneous (due to the skin-damaging effects of excess deposited porphyrins) or neurovisceral attacks of pain, sometimes with weakness, delirium, seizures, and the like (probably due mainly to neurotoxic effects of ALA). The treatment of choice for the acute hepatic porphyrias is intravenous heme therapy, which repletes a critical regulatory heme pool in hepatocytes and leads to downregulation of hepatic ALA synthase, which is a biochemical hallmark of all forms of acute porphyria in relapse. © 2013 American Physiological Society. Compr Physiol 3:365-401, 2013.