Nitrite Reductase Activity and Inhibition of H2S Biogenesis by Human Cystathionine ß-Synthase

摘要: Nitrite was recognized as a potent vasodilator >130 years and has more recently emerged an endogenous signaling molecule modulator of gene expression. Understanding the molecular mechanisms that regulate nitrite metabolism is essential for its use potential diagnostic marker well therapeutic agent cardiovascular diseases. In this study, we have identified human cystathionine s-synthase (CBS) new player in reduction with implications nitrite-dependent control H2S production. This novel activity CBS exploits catalytic property unusual heme cofactor to reduce generate NO. Evidence possible physiological relevance reaction provided by formation ferrous-nitrosyl (FeII-NO) presence NADPH, diflavin methionine synthase reductase (MSR) nitrite. Formation FeII-NO via inhibits CBS, providing avenue regulating biogenesis cysteine, limiting reagent synthesis glutathione, major antioxidant. Our results also suggest role intracellular NO particularly under hypoxic conditions. The participation regulatory unexpected expands repertoire proteins can liberate from pool. reveal mechanism cross-talk between nitrite, biology.