The Mercaptopyruvate Pathway in Cysteine Catabolism: A Physiologic Role and Related Disease of the Multifunctional 3-Mercaptopyruvate Sulfurtransferase

Abstract

The conversion of cysteine to 3-sulfino-alanine is a major pathway in cysteine catabolism. Cysteine dioxygenase catalyzes the reaction and dietary intake of the essential amino acid methionine and the semi-essential amino acid cysteine increases the level of this enzyme by suppressing enzyme degradation via polyubiquitination. The production of cellular antioxidants such as glutathione, thioredoxin, and their families is important in cysteine metabolism, and these cellular antioxidants have critical roles in the maintenance of the cellular redox status. The mercaptopyruvate pathway, in which cysteine or aspartate transaminase catalyzes the transamination from cysteine to 3-mercaptopyruvate and then 3-mercaptopyruvate sulfurtransferase catalyzes the transsulfuration from 3-mercaptopyruvate to pyruvate, also contributes to maintain the cellular redox. 3-Mercaptopyruvate sulfurtransferase serves as an antioxidant protein: when the enzyme is exposed to stoichiometric amounts of the oxidant hydrogen peroxide, it is inhibited via the formation of low redox sulfenate at the catalytic site cysteine. On the other hand, activity is restored by the reductant dithiothreitol or reduced thioredoxin. 3-Mercaptopyruvate sulfurtransferase also detoxifies cyanide via transsulfuration from a stable persulfide at the catalytic site cysteine, a reaction intermediate, suggesting that cyanide detoxification is not necessarily an enzymatic reaction. Furthermore, a congenital defect of the enzyme causes mercaptolactate-cysteine disulfiduria associated with or without mental retardation, although the pathogenesis remains unclear. These facts suggest that 3-mercaptopyruvate sulfurtransferase has physiologic roles as an antioxidant and a cyanide antidote; is essential for neural function, and participates in cysteine degradation.

Impact of a probiotic Enterococcus faecalis in a gnotobiotic mouse model of experimental colitis

“…Mpst is an enzyme that is implemeted in cyanide detoxification [55] and in cysteine catabolism to form pyruvate. Recently, we found Mpst to be downregulated (2.5-fold) in severe E. faecalis OG1RF-induced colitis [49].…”

Thioredoxin-dependent Enzymatic Activation of Mercaptopyruvate Sulfurtransferase

“…On the other hand, rat authentic MST from the liver also had a monomer-dimer equilibrium, with a ratio of ϳ2 to 1 (17). Some oxidants other than dissolved oxygen in the liver tissue might increase the dimer content.…”

“…It is also possible that Trx reacted with Cys 154 and Cys 263 on the surface of MST. MST exhibits monomer-dimer equilibrium (17). The estimated tertiary structure of rat MST (18) using QUANTA/CHARMm (Molecular Simulations Inc., Tokyo, Japan), based on the x-ray structure of bovine rhodanese (19), suggests that Cys 154 and Cys 263 in the hydrophobic patch are too far from each other (32 Å) to form an intrasubunit disulfide bond.…”

Sulfurtransferases 1 and 2 Play Essential Roles in Embryo and Seed Development in Arabidopsis thaliana

“…At this stage, the exact biochemical function of STR1/STR2 in embryo and seed development is unknown. It is possible that they are either directly or indirectly involved in a metabolic pathway that is essential to supply/convert the essential nutrients to support the normal embryogenesis and seed development, based on the putative function of sulfurtransferase in sulfur metabolism (5,6). Alternatively, they could be involved in the removal of a toxic substance produced during the seed-setting stage.…”

“…In animals, sulfurtransferases function in cyanide detoxification (1)(2)(3), hydrogen sulfide detoxification (4), sulfur metabolism (5,6), and synthesis or repair of iron-sulfur proteins (7,8). However, information about their biological functions in plants is limited.…”