ð6:4Þ
In addition to antioxidant chemical species, such as vitamins E and C and
GSH, there are several enzymes, called antioxidant enzymes, that play a pivotal
role in the defense against free-radical-mediated cellular damage. These include
superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(GSHPx), and glutathione reductase. Figure 6.7 shows the interrelationship
between these enzymatic components.
6.6 FACTORS AFFECTING BIOTRANSFORMATION
The activity and levels of each of the P450 enzymes have been shown to vary
between individuals, depending on environmental and genetic factors.
Increased P450 enzyme activity can result from: exposure to xenobiotics or
other environmental factors that induce the synthesis of the enzyme,
stimulation of preexisting enzyme by a xenobiotic, or gene duplication leading
to over expression of a P450 enzyme. Decreased P450 enzyme activity can
occur as a result of: exposure to a xenobiotic capable of inhibiting or
inactivating a preexisting P450 enzyme, exposure to an environmental factor
(such as a xenobiotic) that suppresses P450 enzyme expression, or a mutation
that leads either to blocking the synthesis of a P450 enzyme or to synthesis of
an enzyme with limited activity or total inactivity.
6
For example, in animals many drugs and environmental chemicals can
either stimulate or inhibit microsomal enzymes and so stimulate or inhibit
biotransformation. Chemical agents that can stimulate enzymes include
halogenated hydrocarbon insecticides, urea herbicides, polycyclic aromatic
hydrocarbons (PAHs), nicotine and other alkaloids, and some food preservatives. Agents that can inhibit the enzymes include not only CO, as mentioned
Biotransformation – Metabolism of Xenobiotics
93
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-006.3d]
Ref: 4365 MING-HO YU Chap-006 Page: 93 85-98
FIGURE 6.7 Examples of reactions involving antioxidant enzymes.
In addition to antioxidant chemical species, such as vitamins E and C and
GSH, there are several enzymes, called antioxidant enzymes, that play a pivotal
role in the defense against free-radical-mediated cellular damage. These include
superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(GSHPx), and glutathione reductase. Figure 6.7 shows the interrelationship
between these enzymatic components.
6.6 FACTORS AFFECTING BIOTRANSFORMATION
The activity and levels of each of the P450 enzymes have been shown to vary
between individuals, depending on environmental and genetic factors.
Increased P450 enzyme activity can result from: exposure to xenobiotics or
other environmental factors that induce the synthesis of the enzyme,
stimulation of preexisting enzyme by a xenobiotic, or gene duplication leading
to over expression of a P450 enzyme. Decreased P450 enzyme activity can
occur as a result of: exposure to a xenobiotic capable of inhibiting or
inactivating a preexisting P450 enzyme, exposure to an environmental factor
(such as a xenobiotic) that suppresses P450 enzyme expression, or a mutation
that leads either to blocking the synthesis of a P450 enzyme or to synthesis of
an enzyme with limited activity or total inactivity.
6
For example, in animals many drugs and environmental chemicals can
either stimulate or inhibit microsomal enzymes and so stimulate or inhibit
biotransformation. Chemical agents that can stimulate enzymes include
halogenated hydrocarbon insecticides, urea herbicides, polycyclic aromatic
hydrocarbons (PAHs), nicotine and other alkaloids, and some food preservatives. Agents that can inhibit the enzymes include not only CO, as mentioned
Biotransformation – Metabolism of Xenobiotics
93
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-006.3d]
Ref: 4365 MING-HO YU Chap-006 Page: 93 85-98
FIGURE 6.7 Examples of reactions involving antioxidant enzymes.