Thioredoxin and dihydrolipoic acid are required for 3-mercaptopyruvate sulfurtransferase to produce hydrogen sulfide

Abstract

H2S (hydrogen sulfide) has recently been recognized as a signalling molecule as well as a cytoprotectant. We recently demonstrated that 3MST (3-mercaptopyruvate sulfurtransferase) produces H2S from 3MP (3-mercaptopyruvate). Although a reducing substance is required for an intermediate persulfide at the active site of 3MST to release H2S, the substance has not been identified. In the present study we show that Trx (thioredoxin) and DHLA (dihydrolipoic acid) associate with 3MST to release H2S. Other reducing substances, such as NADPH, NADH, GSH, cysteine and CoA, did not have any effect on the reaction. We also show that 3MST produces H2S from thiosulfate. The present study provides a new insight into a mechanism for the production of H2S by 3MST.

The novel H 2 S-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective effects against ischemia/reperfusion injury through activation of mitoK ATP channels and reduction of oxidative stress

“…extra-mitochondrial calcium) were continuously measured with a calcium-selective mini-electrode, coupled with a reference electrode (WPI, FL, USA), using a data acquisition software (Biopac Inc. California, USA). The selectivity of the electrode for calcium over other cations, such as magnesium, potassium and sodium, is >10 5 . In order to correlate the potentiometric measurements (in mV) with the corresponding concentrations of calcium ions in the solution, calibration curves were generated before each experiment, using known concentrations of CaCl 2 .…”

“…Among these, the regulation of the cardiovascular system is an important role of this gasotransmitter [2,3]. H 2 S is biosynthesized by cystathionine ␤-synthase (CBS), cystathionine ␥-lyase (CSE) [4], and by the cooperation between cysteine aminotransferase (CAT) and 3-mercaptopyruvate sulfurtransferase (MPST) [4][5][6]. The pattern of distribution and localization of these enzymes is quite complex and they may coexist in cardiovascular tissues [7][8][9].…”

A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells

“…Recently, 3-mercaptopyruvate sulfurtransferase (3MST)/cysteine aminotransferase (CAT) pathway has emerged as the third pathway. 3MST produces H 2 S from 3-mercaptopyruvate (3MP), which is generated by CAT from L-cysteine and a-ketoglutarate (a-KG) in the presence of the cofactors thioredoxin and dihydrolipoic acid [14][15][16] . D-Amino acid oxidase (DAO) can also produce achiral a-keto acids, including 3MP, from D-amino acids, some of which are found in mammalian tissues [17][18][19] .…”

Characterization and Interaction Studies of Two Isoforms of the Dual Localized 3-Mercaptopyruvate Sulfurtransferase TUM1 from Humans

“…TUM1 was described to be involved in H 2 S production and signaling, which is also produced by cystathione ␤-synthase and cystathionine ␥-lyase in the cytosol (18). In the TUM1-dependent route for H 2 S generation, 3-MP originating from cysteine is converted to pyruvate and TUM1-bound persulfide, which can be released as H 2 S in the presence of reducing systems like GSH or thioredoxin (19).…”