Abstract
Significance: In recent times, it has emerged that some dietary sulfur compounds can act on mammalian cell signaling systems via their propensity to release hydrogen sulfide (H2S). H2S plays important biochemical and physiological roles in the heart, gastrointestinal tract, brain, kidney, and immune systems of mammals. Reduced levels of H2S in cells and tissues correlate with a spectrum of pathophysiological conditions, including heart disease, diabetes, obesity, and altered immune function. Recent Advances: In the last decade, researchers have now begun to explore the mechanisms by which dietary-derived sulfur compounds, in addition to cysteine, can act as sources of H2S. This research has led to the identified several compounds, organic sulfides, isothiocyanates, and inorganic sulfur species including sulfate that can act as potential sources of H2S in mammalian cells and tissues. Critical Issues: We have summarised progress made in the identification of dietary factors that can impact on endogenous H2S levels in mammals. We also describe current research focused on how some sulfur molecules present in dietary plants, and associated chemical analogues, act as sources of H2S, and discuss the biological properties of these molecules as studied in a range of in vitro and in vivo systems. Future Directions: The identification of sulfur compounds in edible plants that can act as novel H2S releasing molecules is intriguing. Research in this area could inform future studies exploring the impact of diet on H2S levels in mammalian systems. Despite recent progress, additional work is needed to determine the mechanisms by which H2S is released from these molecules following ingestions of dietary plants in humans, whether the amounts of H2S produced is of physiological significance following the metabolism of these compounds in vivo, and if diet could be used to manipulated H2S levels in humans. Importantly, this will lead to a better understanding of the biological significance of H2S generated from dietary sources, and this information could be used in the development of plant breeding initiatives to increase the levels of H2S releasing sulfur compounds in crops, or inform dietary intervention strategies that could be used to alter the levels of H2S in humans.
Highlights
The human diet is composed of a diverse array of inorganic and organic dietary derived sulphur compounds [33]
Changes in the enzymatic routes of synthesis of H2S are clearly important in many metabolic processes and more recent work has indicated that H2S production in mammalian cells can occur via the metabolism of dietary sulfur phytochemicals; a source of H2S largely produced from plant-derived polysulfides [118, 140]
Many sulphur species derived from the diet are metabolised via a spectrum of separate metabolic pathways, leading to the products of sulfur molecules with differing chemical properties
Summary
The human diet is composed of a diverse array of inorganic and organic dietary derived sulphur compounds [33]. Changes in the enzymatic routes of synthesis of H2S are clearly important in many metabolic processes and more recent work has indicated that H2S production in mammalian cells can occur via the metabolism of dietary sulfur phytochemicals; a source of H2S largely produced from plant-derived polysulfides [118, 140]. CBS = Cystathionine β synthase CSE = Cystathionine-γ-lyase 3-MST = 3-Mercaptopyruvate sulfurtransferase SQR-1 = Sulfide–quinone oxidoreductase ETHE1 = Ethylmalonic encephalopathy protein 1 ASCOs = S-alkenyl-L-cysteine sulfoxides GSLs = Glucosinolates ITCs = Isothiocyanates Nrf2 = Nuclear factor erythroid 2-related factor 2 NF-kB = Nuclear factor kappa-light-chain-enhancer of activated B cells SREBP-1 = Sterol regulatory element-binding transcription factor 1 JNK = c-Jun N-terminal kinases GAA = Guanidinoacetic acid PAG = DL-propargylglycine GYY4137 = p-Methoxyphenyl)morpholino-phosphinodithioic acid ATB-346 = H2S-releasing naproxen derivative DATs = Diallyl trisulfide DPDs = Dipropyl disulfide SAC = S-allylcysteine
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