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Hormones, neurotransmitters, growth factors, and other signaling molecules come in different chemical classes. In recent years, a number of gases have been recognized as important messenger molecules. They include nitric oxide, carbon monoxide, and hydrogen sulfide, well known as noxious environmental pollutants, so that their existence in mammals was a surprise. All three normally regulate blood-vessel function and appear to act as neurotransmitters in addition to several other roles. Ways in which they signal to their targets, which is the subject of this Review, differ from the actions of other messenger molecules. Instead of binding to conventional receptors on the external surface of adjacent cells, the gases diffuse into the cells where nitric oxide and carbon monoxide may bind to iron in the enzyme that generates the second messenger molecular cyclic guanosine monophosphate. Nitric oxide and hydrogen sulfide can affect a wide range of proteins both on the cell surface and inside cells by chemically modifying the sulfur atom in the amino acid cysteine.
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