The Heme Oxygenase/Carbon Monoxide System in Hepatobiliary Pathophysiology

  • David Sacerdoti
  • Angelo Gatta


Heme-oxygenase (HO), the rate-limiting enzyme in heme catabolism, was first described in 1968 by Tenhunen et al.1 This enzyme catalyzes the degradation of heme to biliverdin and iron, with the concurrent release of carbon monoxide (CO). In mammals, biliverdin is then converted to bilirubin by the cytosolic enzyme biliverdin reductase; bilirubin is subsequently conjugated with sugars (mainly glucuronic acid) by UDP-glucuronyl transferase and then excreted into the bile. HO is also responsible for the recycling of iron from senescent red blood cells and extra-hematopoietic cells such as liver. Some 80–85% of the bilirubin formed in vivo is derived from hemoglobin released from aging or damaged erythrocytes; this accounts for the high basal activity of HO within those tissues rich in reticuloendothelial cells, such as the spleen and bone marrow. HO mRNA levels are high in fetal rat liver during prenatal maturation (9 days before birth) and reach a maximum 24hrs after birth2 when levels decline but remain above adult levels for at least a month. This correlates with a greater capacity of the liver for bilirubin production in fetuses compared with adults and such circumstances could render the fetus more susceptible to drug injuries because of a depressed heme-cytochrome P450 system. However, Dennery et al.3 found that serum bilirubin protects against serum oxidative damage in the first days of life in noenatal Gunn rats exposed to hypoxia.


Primary Biliary Cirrhosis Heme Oxygenase Primary Biliary Cirrhosis Patient Heme Oxygenase Activity Sinusoidal Tone 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • David Sacerdoti
    • 1
  • Angelo Gatta
    • 1
  1. 1.Department of Clinical and Experimental MedicineUniversity and Azienda Ospedaliera of PadovaVia Giustiniani 2PadovaItaly

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