Hydrogen Sulfide and Hemeproteins: Knowledge and Mysteries

Abstract

Historically, hydrogen sulfide (H(2)S) has been regarded as a poisonous gas, with a wide spectrum of toxic effects. However, like ·NO and CO, H(2)S is now referred to as a signaling gas involved in numerous physiological processes. The list of reports highlighting the physiological effects of H(2)S is rapidly expanding and several drug candidates are now being developed. As with ·NO and CO, not a single H(2)S target responsible for all the biological effects has been found till now. Nevertheless, it has been suggested that H(2)S can bind to hemeproteins, inducing different responses that can mediate its effects. For instance, the interaction of H(2)S with cytochrome c oxidase has been associated with the activation of the ATP-sensitive potassium channels, regulating muscle relaxation. Inhibition of cytochrome c oxidase by H(2)S has also been related to inducing a hibernation-like state. Although H(2)S might induce these effects by interacting with hemeproteins, the mechanisms underlying these interactions are obscure. Therefore, in this review we discuss the current state of knowledge about the interaction of H(2)S with vertebrate and invertebrate hemeproteins and postulate a generalized mechanism. Our goal is to stimulate further research aimed at evaluating plausible mechanisms that explain H(2)S reactivity with hemeproteins.

A Matter of Timing: Contrasting Effects of Hydrogen Sulfide on Oxidative Stress Response in Shewanella oneidensis

“…Using exogenous H 2 S, we demonstrated that it promotes H 2 O 2 killing by specifically damaging heme-containing proteins, especially the CAT KatB, even though it is able to induce the protective OxyR regulon, as described in other bacterial species (3). Such an inhibitory effect on heme-containing proteins such as Cco (mitochondrial aa 3 type), myoglobin, and hemoglobin by H 2 S is well documented in eukaryotes (44)(45)(46). In general, the reaction between these proteins and H 2 S induced modification of the heme component, reversibly inhibiting activity (46,47).…”

“…Such an inhibitory effect on heme-containing proteins such as Cco (mitochondrial aa 3 type), myoglobin, and hemoglobin by H 2 S is well documented in eukaryotes (44)(45)(46). In general, the reaction between these proteins and H 2 S induced modification of the heme component, reversibly inhibiting activity (46,47). Sulfheme species, resulting from the binding of H 2 S, are reduced because of this interaction (48).…”

“…Sulfheme species, resulting from the binding of H 2 S, are reduced because of this interaction (48). Intriguingly, although the inhibitory effect of H 2 S on mitochondrial Cco was first reported more than 80 years ago, the cellular targets of H 2 S are still largely restricted to proteins implicated in oxygen transport and consumption (46). Results presented here clearly show that CATs, at least those from S. oneidensis and bovine liver, and cytochrome cbb 3 oxidase are inactivated by H 2 S, expanding the repertoire of H 2 S targets.…”

“…Nevertheless, with respect to H 2 O 2 killing, CAT is the most crucial target of H 2 S because its loss largely disables the cell's ability to degrade H 2 O 2 . Furthermore, it should be noted that the effect of H 2 S on different heme-containing proteins may vary considerably, given that amino acid residues near the heme play an essential role in sulfheme formation (46).…”

Sulfide Oxidation by a Noncanonical Pathway in Red Blood Cells Generates Thiosulfate and Polysulfides

“…We propose that [1] is in equilibrium with HS ⅐ -Fe II Hb [2]. The latter is also proposed as an intermediate for the sulfide-carrying Hb from L. pectinata (29), and its feasibility is supported by model studies showing that HS Ϫ ligation to ferric porphyrinate generates the corresponding Fe II derivative (30). In principle, the ferrous heme-bound HS ⅐ radical could react with O 2 to form SO 2 .…”