Production of H2S by 3-mercaptopyruvate sulphurtransferase

Hydrogen sulfide (H(2)S) has been established as the third gaseous signaling molecule following nitric oxide and carbon monoxide and participates in a variety of cellular functions such as modulation of neuronal transmission, endothelium-dependent vasorelaxation, stimulation of angiogenesis and regulation of insulin release. Although cystathionine β-synthase and cystathionine γ-lyase have been regarded as the main producers of H(2)S in many tissues including brain, liver and kidney, Kimura and his colleagues have recently communicated that 3-mercaptopyruvate sulphurtransferase coupled with cysteine (aspartate) aminotransferase is responsible for the production of H(2)S in the vascular endothelium of the thoracic aorta [Shibuya et al. (2009) J. Biochem. 146, 623-626]. This finding provides a new insight into the production of the physiologically important signaling molecule.     

Brain foods: the effects of nutrients on brain function

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness.     

Structure and Kinetic Analysis of H2S Production by Human Mercaptopyruvate Sulfurtransferase

Mercaptopyruvate sulfurtransferase (MST) is a source of endogenous H₂S, a gaseous signaling molecule implicated in a wide range of physiological processes. The contribution of MST versus the other two H₂S generators, cystathionine β-synthase and γ-cystathionase, has been difficult to evaluate because many studies on MST have been conducted at high pH and have used varied reaction conditions. In this study, we have expressed, purified, and crystallized human MST in the presence of the substrate 3-mercaptopyruvate (3-MP). The kinetics of H₂S production by MST from 3-MP was studied at pH 7.4 in the presence of various physiological persulfide acceptors: cysteine, dihydrolipoic acid, glutathione, homocysteine, and thioredoxin, and in the presence of cyanide. The crystal structure of MST reveals a mixture of the product complex containing pyruvate and an active site cysteine persulfide (Cys²⁴⁸-SSH) and a nonproductive intermediate in which 3-MP is covalently linked via a disulfide bond to an active site cysteine. The crystal structure analysis allows us to propose a detailed mechanism for MST in which an Asp-His-Ser catalytic triad is positioned to activate the nucleophilic cysteine residue and participate in general acid-base chemistry, whereas our kinetic analysis indicates that thioredoxin is likely to be the major physiological persulfide acceptor for MST.