Reduction of benzoquinones to hydroquinones via spontaneous reaction with glutathione and enzymatic reaction by S-glutathionyl-hydroquinone reductases.
S-Glutathionyl-hydroquinone reductases (GS-HQRs) are a new class of glutathione transferases, widely present in bacteria, halobacteria, fungi, and plants. They catalyze glutathione (GSH)-dependent reduction of GS-trichloro-p-hydroquinone to trichloro-p-hydroquinone. Since GS-trichloro-p-hydroquinone is uncommon in nature, the extensive presence of GS-HQRs suggests they use common GS-hydroquinones. Here we demonstrate that several benzoquinones spontaneously reacted with GSH to form GS-hydroquinones via Michael addition, and four GS-HQRs from yeast and bacteria reduced the GS-hydroquinones to the corresponding hydroquinones. The spontaneous and enzymatic reactions led to the reduction of benzoquinones to hydroquinones with the concomitant oxidation of GSH to oxidized glutathione (GS-SG). The enzymes did not use GS-benzoquinones or other thiol-hydroquinones, for example, S-cysteinyl-hydroquinone, as substrates. Apparent kinetic parameters showed the enzymes preferred hydrophobic, bulky substrates, such as GS-menadiol. The broad substrate range and their wide distribution suggest two potential physiological roles: channeling GS-hydroquinones back to hydroquinones and reducing benzoquinones via spontaneous formation of GS-hydroquinones and then enzymatic reduction to hydroquinones. The functions are likely important in metabolic pathways with quinone intermediates.
School of Molecular Biosciences, Washington State University, Pullman, WA, USA.
L K Metthew
LK
Lam
Zhicheng
Z
Zhang
Philip G
PG
Board
Luying
L
Xun
D016227:Benzoquinones / Q000737:chemistry* / Q000378:metabolism; D020118:Cupriavidus necator / Q000201:enzymology; D005656:Fungal Proteins / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D020075:Phanerochaete / Q000201:enzymology; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D016227:Benzoquinones; D005656:Fungal Proteins; D006873:Hydroquinones; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D005978:Glutathione