Heme oxygenase: the physiological role of one of its metabolites, carbon monoxide and interactions with zinc protoporphyrin, cobalt protoporphyrin and other metalloporphyrins.
In 1991, we postulated that carbon monoxide, which is formed endogenously from heme catabolism catalyzed by heme oxygenase and shares some of the chemical and biological properties of nitric oxide, may play a role similar to that of nitric oxide as a widespread signal transduction mechanism for the regulation of cell function and communication. We review the experimental evidence that tests this postulate. Carbon monoxide appears to be involved in the neurophysiological phenomenon of long-term potentiation, which appears to play a key role in memory and learning. Zinc protoporphyrin, an inhibitor of heme oxygenase, prevents induction of long-term potentiation. Zinc protoporphyrin is an endogenous substance, the levels of which are increased in iron deficiency states and in lead poisoning, and by inhibiting heme oxygenase may modulate long-term potentiation and memory. It has been shown that, when cobalt protoporphyrin is injected into the medial nuclei of the rat hypothalamus, weight loss occurs. These nuclei contain heme oxygenase, and we postulate that weight loss is due to cobalt protoporphyrin induction of heme oxygenase and increased formation of carbon monoxide, which serves as a signal transduction mechanism in the medial hypothalamus to suppress appetite.
Marks
G S
GS
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D006801:Humans; D006932:Hyperbilirubinemia / Q000188:drug therapy; D017774:Long-Term Potentiation / Q000502:physiology; D008665:Metalloporphyrins / Q000378:metabolism / Q000627:therapeutic use; D008670:Metals / Q000633:toxicity; D011524:Protoporphyrins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015431:Weight Loss / Q000502:physiology
D008665:Metalloporphyrins; D008670:Metals; D011524:Protoporphyrins; C017803:zinc protoporphyrin; C007095:cobaltiprotoporphyrin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)