Heme oxygenases are microsomal enzymes that cleave heme to produce the antioxidant biliverdin, inorganic iron and carbon monoxide (CO). The activity of Heme Oxygenase 1 (HO-1), also designated HSP 32, is highly inducible in response to numerous stimuli, including heme, heavy metals, hormones and oxidative stress. Heme Oxygenase 2, in contrast, appears to be constituitively expressed in mammalian tissues. Heme Oxygenase 2 is involved in the production of carbon monoxide (CO) in brain, where CO is thought to act as a neurotransmitter. The CO signaling system closely parallels the signaling pathway involving nitric oxide, and regulation of the two systems is closely linked. Heme Oxygenase 3 is found in the spleen, liver, thymus, prostate, heart, kidney, brain and testis. A poor heme catalyst, Heme Oxygenase 3 has two heme regulatory motifs that may be involved in heme binding.

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