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 endogenou sly from heme catabolism catalyzed by heme oxygenase and shares some o f the chemical and biological properties of nitric oxide, may play a r ole similar to that of nitric oxide as a widespread signal transductio n mechanism for the regulation of cell function and communication. We review the experimental evidence that tests this postulate. Carbon mon oxide appears to be involved in the neurophysiological phenomenon of l ong-term potentiation, which appears to play a key role in memory and learning. Zinc protoporphyrin, an inhibitor of heme oxygenase, prevent s induction of long-term potentiation. Zinc protoporphyrin is an endog enous substance, the levels of which are increased in iron deficiency states and in lead poisoning, and by inhibiting heme oxygenase may mod ulate long-term potentiation and memory. It has been shown that, when cobalt protoporphyrin is injected into the medial nuclei of the rat hy pothalamus, weight loss occurs. These nuclei contain heme oxygenase, a nd we postulate that weight loss is due to cobalt protoporphyrin induc tion of heme oxygenase and increased formation of carbon monoxide, whi ch serves as a signal transduction mechanism in the medial hypothalamu s to suppress appetite.