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Heme oxygenase (HO) is a microsomal enzyme involved in the degradation of heme to biliverdin and carbon monoxide, the former being subsequently converted to bilirubin by the cytosolic biliverdin reductase. Two isoenzymes transcribed from separate genes have been characterized. The HO-2 isoform is constitutively expressed and is present in high concentration in the brain and testes. In contrast, the HO-1 isoform is ubiquitous, found in large quantities in liver and spleen and can be induced by its own substrate, heme, and by a variety of stress-associated agents. Both isoforms of HO are inhibited by metal protoporphyrins such as zinc protoporphyrin IX. CO from HO catalysis has been identified as an endogenous biological messenger in the brain and recent studies suggest its important role in the circulation. Similarly to NO, CO inhibits platelet aggregation and relaxes blood vessels by activating soluble guanylyl cyclase and elevating intracellular levels of cGMP. Locally produced biliverdin and bilirubin are powerful antioxidants and scavengers of free radicals. A change in HO levels has been observed in a wide range of pathophysiological conditions ever since the enzyme was first identified: oxidative stress, resulting from light exposure, free radicals, glutathione depletion, heavy metals, etc., ischemia and hypoxia, inflammation, neonatal jaundice, high blood pressure, diabetes, hematopoiesis, hormonal regulation, development and aging, malarial and other parasitic infections, AIDS, alcohol, cigarette smoke and different xenobiotics. The biological importance of HO stems from its function as the initial and rate-limiting step in heme degradation. The catalytic activity of the system plays a crucial role in maintaining cellular heme homeostasis and hemoprotein levels. The physiological importance of the enzyme stems from its exquisite sensitivity to many chemical agents and pathophysiological conditions. The high expression of HO-1 in response to stress- related factors suggests that heme oxygenase acts as an intracellular protective system against oxidative stress and is essential for adaptation of the organism to the ever-changing internal and external environments.