Table 1.

Overview of Glutathione-Dependent Enzymes

Protein	Fold and family	Glutathione-dependent functiona	Refs.
GR	Pyridine nucleotide disulfide oxidoreductase family	NADPH + H+ + GSSG →2 GSH + NADP+	(60)
		• Link the NADPH pool with the thiol/disulfide pool
		• Reduce GSSG and maintain high GSH concentrations
Grxb	Thioredoxin superfamily	• Catalyze thiol/disulfide exchange reactions (e.g., deglutathionylations or the reduction of ribonucleotide reductase)	(56, 60, 65, 97, 163, 214)
		• Contribute to iron–sulfur cluster biosynthesis
		• Play a regulatory role in iron and redox metabolism
PDIb	Thioredoxin superfamily	• Catalyze thiol/disulfide exchange reactions during oxidative protein folding in the endoplasmic reticulumc	(8, 36, 209, 286)
		• Reduce misfolded substrates of the ERAD pathwayc
		• Act as redox regulator of other proteinsc
GPxb	Thioredoxin superfamily	ROOH + 2 R′SH→R′SS′R + ROH + H2O	(34, 35, 60, 273)
		• Reduce and detoxify hydroperoxides using Trx and/or GSH
		• Act as redox sensor in signal transduction cascades
Prxb	Thioredoxin superfamily	ROOH + 2 R′SH→R′SS′R + ROH + H2O	(34, 60, 113, 238)
		• Reduce hydroperoxides using Trx, Grx, and/or GSH
		• Act as redox sensor in signal transduction cascades
GSTb	Thioredoxin superfamily (or DsbA-liked)	• Conjugate and detoxify drugs, xenobiotics, etc.	(30, 60, 117)
		• Reduce hydroperoxides and/or disulfides
		• Catalyze isomerizations (e.g., during Phe/Tyr-degradation or steroid and eicosanoid metabolism)
		• Exert regulatory functions by protein–protein interaction
MAPEGb	MAPEG domain-like fold	Membrane-associated proteins with divergent functions in eicosanoid and glutathione metabolism:	(60, 135, 176)
		• Catalyze conjugations and (hydro)peroxide reductions
		• Catalyze eicosanoid isomerization and conversions
Glo1	Vicinal oxygen chelate superfamily	• Convert and detoxify 2-oxoaldehydes (isomerase step)	(60, 61, 129, 256, 270)
		• Can have regulatory or unknown functions
Glo2b	β-lactamase fold binuclear metallo-hydrolase family	• Convert and detoxify 2-oxoaldehydes (thioesterase step)	(60, 61, 129, 256, 270)
		• Hydrolyze alternative non-glutathione thioesters
		• Can have regulatory or unknown functions
GSNORe	Alcohol dehydrogenase fold	• Catalyze the NAD+-dependent oxidation of formaldehyde	(24, 173, 260)
		• Catalyze the NADH-dependent reduction of GSNOf
		• Might have regulatory functions

^aPhysiological functions can differ significantly among isoforms and organisms.

^bOrganisms often harbor several isoforms of these proteins.

^cThe relevance of GSH and GSSG for these processes is not fully understood.

^dThe α-helical domain of kappa class GST is inserted and not fused to the Trx domain.

^eIdentical to class III alcohol dehydrogenase (ADH5) or GSH-dependent formaldehyde dehydrogenase.

^fA similar activity was reported for NADPH-dependent human carbonyl reductase 1.

Glo1, glyoxalase 1; Grx, glutaredoxins; GPx, glutathione peroxidase; GR, glutathione reductase; GSNOR, GSNO reductase; GST, glutathione transferase; PDI, protein disulfide isomerase; Prx, peroxiredoxin; ROOH, hydroperoxide; Trx, thioredoxin.