Dealing with Complex Pollution Problems - Organic Pollutants: An Ecotoxicological Perspective - page 247

the activation of galactosidase, the generation of light through the interme-
diacy of reporter genes, and the elevation of mRNA levels. The diversity
of the available bioassays reflects the high profile that endocrine disruptors
have been given in recent years. Some of these assays are described in more
detail in Section 13.5.

6. uncouplers of oxidative phosphorylation. Oxidative phosphorylation of
ADP to generate ATP is a function of the mitochondrial inner membrane
of animals and plants. Compounds that uncouple the process are general
biocides, showing toxicity to animals and plants alike. For oxidative phos-
phorylation to proceed, a proton gradient must be built up across the inner
mitochondrial membrane. The maintenance of a proton gradient depends
on the inner mitochondrial membrane remaining impermeable to protons.
Most uncouplers of oxidative phosphorylation are weak acids that are lipo-
philic when in the undissociated state. Examples include the herbicides
dinitro ortho cresol (DNOC) and dinitro secondary butyl phenol (dinoseb),
and the fungicide pentachlorophenol (PCP). The proton gradients across
inner mitochondrial membranes are built up by active transport, utilizing
energy from the electron transport chain that operates within the membrane.
The direction of the gradient falls from the outside of the membrane to the
inside (Figure 13.1). The dissociated forms (conjugate bases) of the weak
acids combine with protons on the outside of the membrane to form undis-
sociated lipophilic acids, which then dissolve in the membrane and diffuse
across to the inside. Here, where the H + concentration is lower than on the
outside of the membrane, they dissociate to release protons, and so act as
proton translocators. They run down proton gradients, and hence “uncouple”

+

Outside

Inside

-

ADP

An example
of ROH is DNOC

Matrix

ATP Proton gradient

Active transport increases
H + concentration on the
outside

OH

CH 3 NO 2

H +

H +

NO 2

H +

RO -

Uncoupler translocates
proton inward by
diffusion. Proton released
then RO - driven back to
outside by transmembrane
electrochemical potential

ROH
RO - +H +

Inner mitochondrial
membrane

fIgure 13.1 Uncouplers of oxidative phosphorylation.