for example, X(+H+)!HOX, which can do various types of chemistry and
other peroxidases acting on acetaminophen (to generate the quinoneimine),
isoxicam, cyclophophamide, procainamide, and arylamines (Marnett et al.,
1997). These reactions are generally extrahepatic. Some of the products may be
associated with lupus and autoimmune diseases (Miyamoto et al., 1997).
These reactions begin with the formation of a high valent iron complex,
FeO3+(as with P450). Much of the understanding of these systems has been
developed with plant and microbial models, for example, horseradish
peroxidase and (fungal) chloroperoxidase. An initial reaction with an alkyl
hydroperoxide (ROOH) or H 2 O 2 generates ‘‘Compound I’’ (formally FeO3+),
which then abstracts an electron (or possibly a hydrogen atom) from a
substrate to yield ‘‘Compound II,’’ which has a similar oxidation–reduction
potential (Hayashi and Yamazaki, 1979) and may also abstract electrons.
2.5.6 Alcohol Dehydrogenases (ADH)
The general reaction is reversible:
RCH 2 OHþNADþ$RCH¼OþNADHþHþADHs are concentrated in the liver, where these can collectively account for
3% of the total protein (Edenberg and Bosron, 1997). The enzymes have
rather broad specificity for primary and some secondary alcohols. ADHs play
the major role in the metabolism of ethanol in humans.
ADHs are dimers, either heterodimers or homodimers composed of 40 kDa
subunits. Zn2+ is a requirement. At least seven ADH genes are known in
humans (Duester et al., 1999), with other reports of dehydrogenases appearing
(Deng et al., 2002). However, these may be considered a subset of an even
larger superfamily of dehydrogenases (Gonzalez-Duarte and Albalat, 2005).
The different ADH subunits differ in their specificity. Further, a number of
polymorphisms are known that give rise to attenuated function. Some of these
show strong racial linkages. ADHs are inhibited by pyrazole and some similar
compounds.
2.5.7 Aldehyde Dehydrogenases (ALDH)
ALDHs catalyze the oxidation of aldehydes to carboxylic acids, which is
usually not reversible:
RCHOþNADþ!RCO 2 HþNADHþHþ
The reaction can be compared with that of the aldehyde oxidase (vide supra)RCHOþH 2 OþO 2 !RCO 2 HþH 2 O 2The ALDHs are concentrated in the liver, mainly in the mitochondria
(Petersen and Lindahl, 1997). The human genome contains 19 putatively
OXIDATION ENZYMES 25