Similarly, iminoquinones can be reduced, and the enzymes can also reduce
nitro compounds and azo dyes (Ross, 1997).
NQO1 was first characterized as ‘‘DT diaphorase,’’ with diaphorase being
an older term for an enzyme that catalyzes electron transfer from pyridine
nucleotides. ‘‘DT’’ indicated that this enzyme could accept electrons from
NADH (formerly termed DPNH) or NADPH (formerly TPNH). Some of the
other early work was unclear but the location of the enzyme is cytosolic
(Huang et al., 1979). This is a flavoprotein that reduces substrates. In contrast
to NADPH-P450 reductase, most NQO reactions are 2-electron reductions,
avoiding the generation of radicals. However, the product hydroquinones may
react with O 2 to generate O 2 .
NQOl is inducible via both the Ah receptor and the ARE pathways (Ross,
1997). Dicoumarol is a long-established potent inhibitor of NQO. A second
gene, NQO2; is found in humans (Jaiswal, 1994). A related p53-regulated gene
with considerable sequence identity has been discovered (PIG3) (Nicholls et al.,
2004) but no redox function has yet been identified.
2.6.5 Glutathione Peroxidase (GPX)
These enzyme systems reduce potentially toxic organic hydroperoxides,
including H 2 O 2 :
2GSHþROOH!GSSGþROHThe reaction is coupled to the regeneration of GSH by GSH reductaseNADPHþHþþGSSG!NADPþþ2GSHThe net process can be written asNADPHþHþþROOH!NADPþþROHSix human GSH peroxidases have been identified. Most of the enzymes
contain selenocysteine in the active site, with the exceptions of GPX 5 and 6
(Burk, 1997). Some GSH transferase enzymes also display low GSH peroxidase
activity (Ketterer and Meyer, 1989). Thioredoxin, a lowMriron–sulfur protein,
can also transfer electrons (instead of GSH in some cases). Some GSH
peroxidases are extracellular and function in plasma.
2.7 Hydrolysis
2.7.1 Epoxide Hydrolase
Epoxides are reactive electrophiles by nature of their ring strain and change
localization; they vary considerably in stability and reactivity (Guengerich,
HYDROLYSIS 29